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Background: Three-dimensional (3D) T1-weighted MRI sequences such as the magnetization prepared rapid gradient echo (MPRAGE) sequence are important for assessing regional cortical atrophy in the clinical evaluation of dementia but have long acquisition times and are prone to motion artifact. The recently developed Scout Accelerated Motion Estimation and Reduction (SAMER) retrospective motion correction method addresses motion artifact within clinically-acceptable computation times and has been validated through qualitative evaluation in inpatient and emergency settings., Methods: We evaluated the quantitative accuracy of morphometric analysis of SAMER motion-corrected compared to non-motion-corrected MPRAGE images by estimating cortical volume and thickness across neuroanatomical regions in two subject groups: (1) healthy volunteers and (2) patients undergoing evaluation for dementia. In part (1), we used a set of 108 MPRAGE reconstructed images derived from 12 healthy volunteers to systematically assess the effectiveness of SAMER in correcting varying degrees of motion corruption, ranging from mild to severe. In part (2), 29 patients who were scheduled for brain MRI with memory loss protocol and had motion corruption on their clinical MPRAGE scans were prospectively enrolled., Results: In part (1), SAMER resulted in effective correction of motion-induced cortical volume and thickness reductions. We observed systematic increases in the estimated cortical volume and thickness across all neuroanatomical regions and a relative reduction in percent error values compared to reference standard scans of up to 66 % for the cerebral white matter volume. In part (2), SAMER resulted in statistically significant volume increases across anatomical regions, with the most pronounced increases seen in the parietal and temporal lobes, and general reductions in percent error relative to reference standard clinical scans., Conclusion: SAMER improves the accuracy of morphometry through systematic increases and recovery of the estimated cortical volume and cortical thickness following motion correction, which may affect the evaluation of regional cortical atrophy in patients undergoing evaluation for dementia., Competing Interests: Declaration of competing interest Authors Wei-Ching Lo and Bryan Clifford are employees of Siemens Medical Solutions USA. Authors Daniel Polak and Daniel Nicolas Splitthoff are employees of Siemens Healthineers., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Objective: The pathophysiology behind memory impairment in Parkinson's Disease Mild Cognitive Impairment (PD-MCI) is unclear. This study aims to investigate the hippocampal and cortical atrophy patterns in PD-MCI patients with different types of memory impairments, categorized as Retrieval Failure (RF) and Encoding Failure (EF)., Methods: The study included 16 healthy controls (HC) and 34 PD-MCI patients, divided into RF (N = 18) and EF (N = 16) groups based on their Verbal Memory Processes Test (VMPT) scores, including spontaneous recall, recognition, and Index of Sensitivity to Cueing (ISC). Hippocampal subfields and cortical thicknesses were measured using the FreeSurfer software for automatic segmentation., Results: Compared to the HC group, the EF group exhibited significant atrophy in the left lateral occipital region and the right caudal middle frontal, superior temporal, and inferior temporal regions (p⟨0.05). The RF group displayed significant atrophy in the left lateral occipital, middle temporal, and precentral regions, as well as the right pars orbitalis and superior frontal regions (p⟨0.05). Hippocampal subfield analysis revealed distinct volume differences between HC-EF and RF-EF groups, with significant reductions in the CA1, CA3, and CA4 subregions in the EF group, but no differences between HC and RF groups (p > 0.05)., Conclusion: Gray matter atrophy patterns differ in PD-MCI patients with encoding and retrieval memory impairments. The significant hippocampal atrophy in the EF group, particularly in the CA subregions, highlights its potential role in disease progression and memory decline. Additionally, the convergence of atrophy in the lateral occipital cortex across both RF and EF groups suggests the involvement of the Parietal Memory Network (PMN) in PD-related memory impairment., (© 2024 The Author(s). CNS Neuroscience & Therapeutics published by John Wiley & Sons Ltd.)

In medial temporal lobe epilepsy (MTLE), the benefits of surgery must be balanced against the risk of post-operative memory decline. Prediction of postoperative outcomes based on functional magnetic resonance imaging (fMRI) tasks is increasingly common but remains uncertain. The aim of this retrospective study was to determine whether hippocampal activations elicited by fMRI language tasks could enhance or refine memory fMRI in MTLE patients candidates to surgery. Forty-six patients were included: 30 right and 16 left MTLE, mostly with hippocampal sclerosis. Preoperative assessment included neuropsychological tests and fMRI with language (syntactic verbal fluency) and memory tasks (encoding, delayed, and immediate recognition of images of objects). Thirty patients underwent surgery and had neuropsychological evaluations one year after surgery. Worsening was defined as a degradation of more than 10 % in postoperative forgetting scores compared to preoperative scores in verbal, non-verbal and global memory. Memory fMRI had the best sensitivity with hippocampal activations obtained in 95 % of patients, versus 65 % with language fMRI. Considering the patients who elicited an hippocampal activation, language fMRI led to 80 %, 65 % and 85 % of correct predictions for respectively global, verbal and non verbal memory (versus 71 %, 64 % and 68 % with memory fMRI). Memory and language fMRI predictions outperformed those made by neuropsychological tests. In summary, language fMRI was less sensitive than memory fMRI to elicit hippocampal activations but when it did, the proportion of correct memory predictions was better. Moreover, it proved to be an independent predictive factor regardless of the side of the epileptic focus. Given the ease of setting up a language task in fMRI, we recommend the systematic combination of memory and language tasks to predict the post-operative memory outcome of MTLE patients undergoing epilepsy surgery., Competing Interests: Declaration of Competing Interest The authors have no conflict of interest to disclose. This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is characterized by distinct structural and functional brain alterations, predominantly affecting the medial temporal lobes and the hippocampus. Structural connectome analysis with graph-based investigations of network properties allows for an in-depth characterization of global and local network changes and their relationship with clinical deficits in NMDAR encephalitis., Methods: Structural networks from 61 NMDAR encephalitis patients in the post-acute stage (median time from acute hospital discharge: 18 months) and 61 age- and sex-matched healthy controls (HC) were analyzed using diffusion-weighted imaging (DWI)-based probabilistic anatomically constrained tractography and volumetry of a selection of subcortical and white matter brain volumes was performed. We calculated global, modular, and nodal graph measures with special focus on default-mode network, medial temporal lobe, and hippocampus. Pathologically altered metrics were investigated regarding their potential association with clinical course, disease severity, and cognitive outcome., Results: Patients with NMDAR encephalitis showed regular global graph metrics, but bilateral reductions of hippocampal node strength (left: p = 0.049; right: p = 0.013) and increased node strength of right precuneus (p = 0.013) compared to HC. Betweenness centrality was decreased for left-sided entorhinal cortex (p = 0.042) and left caudal middle frontal gyrus (p = 0.037). Correlation analyses showed a significant association between reduced left hippocampal node strength and verbal long-term memory impairment (p = 0.021). We found decreased left (p = 0.013) and right (p = 0.001) hippocampal volumes that were associated with hippocampal node strength (left p = 0.009; right p < 0.001)., Conclusions: Focal network property changes of the medial temporal lobes indicate hippocampal hub failure that is associated with memory impairment in NMDAR encephalitis at the post-acute stage, while global structural network properties remain unaltered. Graph theory analysis provides new pathophysiological insight into structural network changes and their association with persistent cognitive deficits in NMDAR encephalitis., (© 2024. The Author(s).)

Background: Addiction can alter neural processes during rest and cognitive performance. Subjects with addictive disorders exhibit preoccupation and anticipation for the psychoactive substance when idle and cognitive deficits, during tasks., Methods: 128 channel EEG was recorded in sixty subjects (30, with alcohol, opioid and internet addiction; 30 controls) during rest and while performing working memory task to ascertain underlying differences in cortical activity between the groups while at rest and during performance of the task. Artifactually clean data was then subjected to source analysis using sLORETA software in both the groups., Results: EEG cortical source analysis in subjects with addictive disorders showed significant activation of areas of Default Mode Network (DMN) and reduced activation in dorsolateral prefrontal cortices (DLPFC), an area known to be involved in executive function, during performance of task. However, control subjects demonstrated significantly reduced activation in areas of DMN; and increased activation of DLPFC during task performance., Conclusion: Inability to suppress DMN inhibits reallocation of neural resources to areas of executive functioning leading to working memory deficits in subjects with addictive disorder., Competing Interests: Declaration of competing interest No competing financial interests exist between authors Shaon Ghosh Dastidar, Nishi Pegwal, Yatan Pal Singh Balhara, Prashant Tayade, Ratna Sharma and Simran Kaur that could have appeared to influence the work reported in this article., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Importance: Studies have suggested that maternal history of late-onset Alzheimer disease, but not paternal, predisposes individuals to higher brain β-amyloid (Aβ) burden, reduced brain metabolism, and lower gray matter volumes., Objective: To characterize maternal vs paternal history of memory impairment in terms of brain Aβ-positron emission tomography (Aβ-PET) and baseline cognition among a large sample of cognitively unimpaired older adults., Design, Setting, and Participants: This cross-sectional study leveraged data from 4413 individuals who were screened for the Anti-Amyloid Treatment in Asymptomatic Alzheimer (A4) study, a randomized clinical trial conducted across 67 sites in the US, Australia, Canada, and Japan aimed at Alzheimer disease prevention. Data were collected between April 2014 and December 2017 and analyzed from December 2022 to June 2023. Participants were cognitively unimpaired adults (Clinical Dementia Rating = 0 and/or Mini-Mental State Examination score ≥25) between the ages of 65 and 85 years who underwent PET imaging to assess cortical Aβ levels for trial eligibility. A total of 4492 participants were screened, and 79 missing data were excluded., Main Outcomes and Measures: Demographic characteristics (eg, age, sex, education), apolipoprotein E genotyping, participant-reported parental history of memory impairment and parental age at symptom onset were collected as variables. Parental history was assessed in terms of continuous neocortical 18F-florbetapir Aβ-PET and the Preclinical Alzheimer Cognitive Composite., Results: Of 4413 individuals (mean [SD] age, 71.27 [4.66] years, 2617 women [59.3%]), mean Aβ-PET was elevated in individuals with history of memory impairment in both parents (n = 455; mean [SD] standardized uptake value ratio [SUVR] = 1.12 [0.19]; Wilcoxon P = 1.1 × 10-5) and in those with only maternal history (n = 1772; mean [SD] SUVR = 1.10 [0.19]; Wilcoxon P = 2.70 × 10-5) compared with those with only paternal history (n = 632; mean [SD] SUVR = 1.08 [0.18]; Wilcoxon P = 1.1 × 10-5) or no family history (n = 1554; mean [SD] SUVR = 1.08 [0.19]; Wilcoxon P = 1.1 × 10-5). Paternal history of early-onset memory impairment (age <65 years) but not late-onset (age ≥65 years) was associated with elevated participant Aβ-PET (mean [SD] SUVR = 1.19 [0.21]; P = 3.00 × 10-6) in comparison with no paternal history (mean [SD] SUVR = 1.09 [0.19]) whereas maternal history was associated with elevated Aβ in both early-onset and late-onset groups. There was no association with cognition., Conclusions and Relevance: In this study, maternal history (at any age) and paternal history of early-onset memory impairment were associated with Aβ burden among asymptomatic older individuals. Sex-specific parental history may help inform clinicians on likelihood of Aβ burden in offspring and help identify high-risk individuals at the earliest stages of disease for prevention.

Background: Research work has shown that hippocampal subfields are atrophic to varying extents in multiple sclerosis (MS) patients. However, studies examining the functional implications of subfield-specific hippocampal damage in early MS are limited. We aim to gain insights into the relationship between hippocampal atrophy and memory function by investigating the correlation between global and regional hippocampal atrophy and memory performance in early MS patients., Methods: From the Italian Neuroimaging Network Initiative (INNI) dataset, we selected 3D-T1-weighted brain MRIs of 219 early relapsing remitting (RR)MS and 246 healthy controls (HC) to identify hippocampal atrophic areas. At the time of MRI, patients underwent Selective-Reminding-Test (SRT) and Spatial-Recall-Test (SPART) and were classified as mildly (MMI-MS: n.110) or severely (SMI-MS: n:109) memory impaired, according to recently proposed cognitive phenotypes., Results: Early RRMS showed lower hippocampal volumes compared to HC (p < 0.001), while these did not differ between MMI-MS and SMI-MS. In MMI-MS, lower hippocampal volumes correlated with worse memory tests (r = 0.23-0.37, p ≤ 0.01). Atrophic voxels were diffuse in the hippocampus but more prevalent in cornu ammonis (CA, 79%) than in tail (21%). In MMI-MS, decreased subfield volumes correlated with decreases in memory, particularly in the right CA1 (SRT-recall: r = 0.38; SPART: r = 0.34, p < 0.01). No correlations were found in the SMI-MS group., Conclusion: Hippocampal atrophy spreads from CA to tail from early disease stages. Subfield hippocampal atrophy is associated with memory impairment in MMI-MS, while this correlation is lost in SMI-MS. This plays in favor of a limited capacity for an adaptive functional reorganization of the hippocampi in MS patients., (© 2024. The Author(s).)

The etiology of brain fog associated with long COVID is not clear. Based on some preliminary work, disruption of the blood-brain barrier has been hypothesized, but has not been tested in patients with long COVID. In this case-control pilot study, we evaluated blood-brain barrier permeability in patients with long COVID and subjective memory loss or brain fog. We used 99 m Technetium diethylenetriaminepentaacetic acid single-photon emission computed tomography (SPECT) to measure blood-brain barrier permeability and a telephone assessment (T-cog) to measure cognitive function. The blood-brain barrier permeability was quantified via SPECT standard uptake value (SUV). We assessed the blood-brain barrier permeability in 14 long COVID patients and 10 control participants without subjective cognitive impairment or brain fog. Participants in the two groups were similar in age. The long COVID group had more comorbidities compared to the control group. There was no difference in the SUVs in the long COVID (0.22 ± 0.12) vs the control (0.17 ± 0.04) group. There was no difference in the T-cog results in the two groups either. We found no evidence of a difference in blood-brain permeability in patients with long COVID when compared to controls without a known history of COVID-19 infection. Larger studies are needed to confirm these findings., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background and Purpose: Verbal memory decline is a common complaint of patients with severe asymptomatic stenosis of the internal carotid artery (aICS). Previous publications explored the associations between verbal memory decline and altered functional connectivity (FC) after aICS. Patients with severe aICS may show reduced perfusion in the ipsilateral territory and redistribution of cerebral blood flow to compensate for the deficient regions, including expansion of the posterior and contralateral ICA territories via the circle of Willis. However, aICS-related FC changes in anterior and posterior territories and the impact of the sides of stenosis were less explored. This study aims to investigate the altered FC in anterior and posterior circulation territories of patients with left or right unilateral aICS and its association with verbal memory decline., Materials and Methods: We enrolled 15 healthy controls (HCs), 22 patients with left aICS (aICS L ), and 33 patients with right aICS (aICS R ) to receive fMRI, Mini-Mental State Examination (MMSE), the Digit Span Test (DST), and the 12-item Chinese version of Verbal Learning Tests. We selected brain regions associated with verbal memory within anterior and posterior circulation territories. Territory-related FC alterations and verbal memory decline were identified by comparing the aICS L and aICS R groups with HC groups ( P  < .05, corrected for multiple comparisons), respectively. Furthermore, the association between altered FC and verbal memory decline was tested with the Pearson correlation analysis., Results: Compared with HCs, patients with aICS L or aICS R had significant impairment in delayed recall of verbal memory. Decline in delayed recall of verbal memory was significantly associated with altered FC between the right cerebellum and right middle temporal pole in the posterior circulation territory ( r  = 0.40, P  = .03) in the aICS R group and was significantly associated with altered FC between the right superior medial frontal gyrus and left lingual gyrus in the anterior circulation territory ( r  = 0.56, P = .01) in the aICS L group., Conclusions: Patients with aICS L and aICS R showed different patterns of FC alterations in both anterior and posterior circulation territories, which suggests that the side of aICS influences the compensatory mechanism for decline in delayed recall of verbal memory., (© 2024 by American Journal of Neuroradiology.)

Schizophrenia, as a chronic and persistent disorder, exhibits working memory deficits across various stages of the disorder, yet the neural mechanisms underlying these deficits remain elusive with inconsistent neuroimaging findings. We aimed to compare the brain functional changes of working memory in patients at different stages: clinical high risk, first-episode psychosis, and long-term schizophrenia, using meta-analyses of functional magnetic resonance imaging studies. Following a systematic literature search, 56 whole-brain task-based functional magnetic resonance imaging studies (15 for clinical high risk, 16 for first-episode psychosis, and 25 for long-term schizophrenia) were included. The separate and pooled neurofunctional mechanisms among clinical high risk, first-episode psychosis, and long-term schizophrenia were generated by Seed-based d Mapping toolbox. The clinical high risk and first-episode psychosis groups exhibited overlapping hypoactivation in the right inferior parietal lobule, right middle frontal gyrus, and left superior parietal lobule, indicating key lesion sites in the early phase of schizophrenia. Individuals with first-episode psychosis showed lower activation in left inferior parietal lobule than those with long-term schizophrenia, reflecting a possible recovery process or more neural inefficiency. We concluded that SCZ represent as a continuum in the early stage of illness progression, while the neural bases are inversely changed with the development of illness course to long-term course., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: The mechanisms underlying memory deficits after electroconvulsive therapy (ECT) remain unclear but altered functional interactions between hippocampus and neocortex may play a role., Objectives: To test whether ECT reduces functional connectivity between hippocampus and posterior regions of the default mode network (DMN) and to examine whether altered hippocampal-neocortical functional connectivity correlates with memory impairment. A secondary aim was to explore if these connectivity changes are present 6 months after ECT., Methods: In-patients with severe depression (n = 35) received bitemporal ECT. Functional connectivity of the hippocampus was probed with resting-state fMRI before the first ECT-session, after the end of ECT, and at a six-month follow-up. Memory was assessed with the Verbal Learning Test - Delayed Recall. Seed-based connectivity analyses established connectivity of four hippocampal seeds, covering the anterior and posterior parts of the right and left hippocampus., Results: Compared to baseline, three of four hippocampal seeds became less connected to the core nodes of the posterior DMN in the week after ECT with Cohen's d ranging from -0.9 to -1.1. At the group level, patients showed post-ECT memory impairment, but individual changes in delayed recall were not correlated with the reduction in hippocampus-DMN connectivity. At six-month follow-up, no significant hippocampus-DMN reductions in connectivity were evident relative to pre-ECT, and memory scores had returned to baseline., Conclusion: ECT leads to a temporary disruption of functional hippocampus-DMN connectivity in patients with severe depression, but the change in connectivity strength is not related to the individual memory impairment., Competing Interests: Declaration of competing interest Krzysztof Gbyl disclosed unrestricted grants from the following fonds: Augustinusfonden, Axel Muusfeldts Fond, Beckett-Fonden, A.P. Møller Fonden: Fonden til Lægevidenskabens Fremme, Helsefonden, Ivan Nielsens Fond for personer med specielle sindslidelser, Jascha Fonden, Læge Gerhard Linds Legat, Lundbeckfonden, Psykiatrisk Forskningsfond af 1967, and Region Hovedstaden Fond. Hartwig R. Siebner has received honoraria as speaker and consultant from Lundbeck AS, Denmark, and as editor (Neuroimage Clinical) from Elsevier Publishers, Amsterdam, The Netherlands. He has received royalties as book editor from Springer Publishers, Stuttgart, Germany, Oxford University Press, Oxford, UK, and from Gyldendal Publishers, Copenhagen, Denmark. Christoffer Cramer Lundsgaard disclosed an honorarium from Lundbeck Pharma A/S. Remaining authors Vytautas Labanauskas, André Mathiassen, Adam Ryszczuk, Egill Rostrup, Kristoffer Madsen, and Poul Videbech declared no biomedical financial or other potential conflict of interests., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Cognitive impairment (CI) is a common and disabling feature of people with multiple sclerosis (pwMS), but its underlying mechanisms are heterogenous and not fully understood. A role of infiltrating immune cells in the meninges and brain parenchyma has been hypothesized. This study aimed to explore the hypothesis that intrathecal B cells might influence cognitive performance in pwMS., Methods: A retrospective study was performed on 39 newly diagnosed pwMS who underwent cerebrospinal fluid (CSF) analysis. Kappa (κ)-index was measured as a biomarker of intrathecal B cell activation. Cognitive performance was assessed using the Brief Repeatable Battery of Neuropsychological Tests (BRBN). Brain T2 lesions number (T2LN) and volume (T2LV) together with brain, cortical grey matter, thalamic and hippocampal volumes were calculated to account for MRI-visible damage., Results: κ-index was higher in pwMS with verbal memory impairment (median 99.6, range 58.5-195.2 vs. median 37.2, range 2.3-396.9, p < 0.001), and it was negatively associated with BRBN tests exploring verbal memory and information processing speed. In multivariate models, higher κ-index was confirmed to be independently associated with worse scores of BRBN tests exploring verbal memory and with a higher probability of verbal memory impairment., Conclusion: Intrathecal B cells might drive memory impairment in pwMS independently of brain damage visible on MRI scans., Competing Interests: Declaration of competing interest LG participated on advisory boards for, and received writing honoraria and travel grants from Almirall, Biogen, Euroimmun, Fujirebio, Lilly, Merck, Mylan, Novartis, Roche, Sanofi, Siemens Healthineers and Teva. AM participated on advisory boards for, and received writing honoraria and travel grants to attend national and international conferences from Alexion, Almirall, Biogen Idec, Merck, Mylan, Novartis, Sanofi and Teva. NDS participated on advisory boards for and received speaker or writing honoraria and funding for travelling from Bayer, Biogen Idec, Bristol, Genzyme, Immunic, Merck, Novartis, Roche, and Teva. MDF participated on advisory boards and steering committees for and received speaker or writing honoraria, research support and funding for travelling from Alexion, BMS, Bayer, Biogen Idec, Genzyme, Horizon, Janssen, Merck, Mylan, Novartis, Roche, Siemens Healthineers, Teva and Viatris. NS, GB, SS, AF, EDS, AV, and LP report no conflict of interest., (Copyright © 2024. Published by Elsevier B.V.)

Verbal memory decline is a significant concern following temporal lobe surgeries in patients with epilepsy, emphasizing the need for precision presurgical verbal memory mapping to optimize functional outcomes. However, the inter-individual variability in functional networks and brain function-structural dissociations pose challenges when relying solely on group-level atlases or anatomical landmarks for surgical guidance. Here, we aimed to develop and validate a personalized functional mapping technique for verbal memory using precision resting-state functional MRI (rs-fMRI) and neurosurgery. A total of 38 patients with refractory epilepsy scheduled for surgical interventions were enrolled and 28 patients were analyzed in the study. Baseline 30-min rs-fMRI scanning, verbal memory and language assessments were collected for each patient before surgery. Personalized verbal memory networks (PVMN) were delineated based on preoperative rs-fMRI data for each patient. The accuracy of PVMN was assessed by comparing post-operative functional impairments and the overlapping extent between PVMN and surgical lesions. A total of 14 out of 28 patients experienced clinically meaningful declines in verbal memory after surgery. The personalized network and the group-level atlas exhibited 100% and 75.0% accuracy in predicting postoperative verbal memory declines, respectively. Moreover, six patients with extra-temporal lesions that overlapped with PVMN showed selective impairments in verbal memory. Furthermore, the lesioned ratio of the personalized network rather than the group-level atlas was significantly correlated with postoperative declines in verbal memory (personalized networks: r = -0.39, p = .038; group-level atlas: r = -0.19, p = .332). In conclusion, our personalized functional mapping technique, using precision rs-fMRI, offers valuable insights into individual variability in the verbal memory network and holds promise in precision verbal memory network mapping in individuals., (© 2024 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.)

Introduction: In Alzheimer's disease (AD), early diagnosis facilitates treatment options and leads to beneficial outcomes for patients, their carers and the healthcare system. The neuropsychological battery of the Uniform Data Set (UDSNB3.0) assesses cognition in ageing and dementia, by measuring scores across different cognitive domains such as attention, memory, processing speed, executive function and language. However, its neuroanatomical correlates have not been investigated using 7 Tesla MRI (7T MRI)., Methods: We used 7T MRI to investigate the correlations between hippocampal subfield volumes and the UDSNB3.0 in 24 individuals with Amyloidβ-status AD and 18 age-matched controls, with respective age ranges of 60 (42-76) and 62 (52-79) years. AD participants with a Medial Temporal Atrophy scale of higher than 2 on 3T MRI were excluded from the study., Results: A significant difference in the entire hippocampal volume was observed in the AD group compared to healthy controls (HC), primarily influenced by CA1, the largest hippocampal subfield. Notably, no significant difference in whole brain volume between the groups implied that hippocampal volume loss was not merely reflective of overall brain atrophy. UDSNB3.0 cognitive scores showed significant differences between AD and HC, particularly in Memory, Language, and Visuospatial domains. The volume of the Dentate Gyrus (DG) showed a significant association with the Memory and Executive domain scores in AD patients as assessed by the UDSNB3.0.. The data also suggested a non-significant trend for CA1 volume associated with UDSNB3.0 Memory, Executive, and Language domain scores in AD. In a reassessment focusing on hippocampal subfields and MoCA memory subdomains in AD, associations were observed between the DG and Cued, Uncued, and Recognition Memory subscores, whereas CA1 and Tail showed associations only with Cued memory., Discussion: This study reveals differences in the hippocampal volumes measured using 7T MRI, between individuals with early symptomatic AD compared with healthy controls. This highlights the potential of 7T MRI as a valuable tool for early AD diagnosis and the real-time monitoring of AD progression and treatment efficacy., Clinicaltrials: GOV: ID NCT04992975 (Clinicaltrial.gov 2023)., Competing Interests: Declaration of competing interest None of the authors have conflict of interest., (Copyright © 2024. Published by Elsevier Inc.)

Dopamine decline is suggested to underlie aging-related cognitive decline, but longitudinal examinations of this link are currently missing. We analyzed 5-year longitudinal data for a sample of healthy, older adults (baseline: n = 181, age: 64-68 years; 5-year follow-up: n = 129) who underwent positron emission tomography with 11 C-raclopride to assess dopamine D2-like receptor (DRD2) availability, magnetic resonance imaging to evaluate structural brain measures, and cognitive tests. Health, lifestyle, and genetic data were also collected. A data-driven approach (k-means cluster analysis) identified groups that differed maximally in DRD2 decline rates in age-sensitive brain regions. One group (n = 47) had DRD2 decline exclusively in the caudate and no cognitive decline. A second group (n = 72) had more wide-ranged DRD2 decline in putamen and nucleus accumbens and also in extrastriatal regions. The latter group showed significant 5-year working memory decline that correlated with putamen DRD2 decline, along with higher dementia and cardiovascular risk and a faster biological pace of aging. Taken together, for individuals with more extensive DRD2 decline, dopamine decline is associated with memory decline in aging., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Cerebral small vessel disease is the one of the most prevalent causes of vascular cognitive impairment. We aimed to find objective and process-based indicators related to memory function to assist in the detection of memory impairment in patients with cerebral small vessel disease. Thirty-nine cerebral small vessel disease patients and 22 healthy controls were invited to complete neurological examinations, neuropsychological assessments, and eye tracking tasks. Eye tracking indicators were recorded and analyzed in combination with imaging features. The cerebral small vessel disease patients scored lower on traditional memory task and performed worse on eye tracking memory task performance compared to the healthy controls. The cerebral small vessel disease patients exhibited longer visit duration and more visit count within areas of interest and targets and decreased percentage value of total visit duration on target images to total visit duration on areas of interest during decoding stage among all levels. Our results demonstrated the cerebral small vessel disease patients performed worse in memory scale and eye tracking memory task, potentially due to their heightened attentional allocation to nontarget images during the retrieval stage. The eye tracking memory task could provide process-based indicators to be a beneficial complement to memory assessment and new insights into mechanism of memory impairment in cerebral small vessel disease patients., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permission@oup.com.)

Background: We compared the ability of several plasma biomarkers versus amyloid positron emission tomography (PET) to predict rates of memory decline among cognitively unimpaired individuals., Methods: We studied 645 Mayo Clinic Study of Aging participants. Predictor variables were age, sex, education, apolipoprotein E (APOE) ε4 genotype, amyloid PET, and plasma amyloid beta (Aβ)42/40, phosphorylated tau (p-tau)181, neurofilament light (NfL), glial fibrillary acidic protein (GFAP), and p-tau217. The outcome was a change in a memory composite measure., Results: All plasma biomarkers, except NfL, were associated with mean memory decline in models with individual biomarkers. However, amyloid PET and plasma p-tau217, along with age, were key variables independently associated with mean memory decline in models combining all predictors. Confidence intervals were narrow for estimates of population mean prediction, but person-level prediction intervals were wide., Discussion: Plasma p-tau217 and amyloid PET provide useful information about predicting rates of future cognitive decline in cognitively unimpaired individuals at the population mean level, but not at the individual person level., (© 2024 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

Aim: The three-phase enriched environment (EE) intervention paradigm has been shown to improve learning and memory function after cerebral ischemia, but the neuronal mechanisms are still unclear. This study aimed to investigate the hippocampal-cortical connectivity and the metabolic interactions between neurons and astrocytes to elucidate the underlying mechanisms of EE-induced memory improvement after stroke., Methods: Rats were subjected to permanent middle cerebral artery occlusion (pMCAO) or sham surgery and housed in standard environment or EE for 30 days. Memory function was examined by Morris water maze (MWM) test. Magnetic resonance imaging (MRI) was conducted to detect the structural and functional changes. [ 18 F]-fluorodeoxyglucose (FDG) positron emission tomography (PET) was conducted to detect brain energy metabolism. PET-based brain connectivity and network analysis was performed to study the changes of hippocampal-cortical connectivity. Astrocyte-neuron metabolic coupling, including gap junction protein connexin 43 (Cx43), glucose transporters (GLUTs), and monocarboxylate transporters (MCTs), was detected by histological studies., Results: Our results showed EE promoted memory function improvement, protected structure integrity, and benefited energy metabolism after stroke. More importantly, EE intervention significantly increased functional connectivity between the hippocampus and peri-hippocampal cortical regions, and specifically regulated the level of Cx43, GLUTs and MCTs in the hippocampus and cortex., Conclusions: Our results revealed the three-phase enriched environment paradigm enhanced hippocampal-cortical connectivity plasticity and ameliorated post-stroke memory deficits. These findings might provide some new clues for the development of EE and thus facilitate the clinical transformation of EE., (© 2023 The Authors. CNS Neuroscience & Therapeutics published by John Wiley & Sons Ltd.)

Objective: Neuroimaging studies reveal frontal lobe (FL) contributions to memory encoding. Accordingly, memory impairments are documented in frontal lobe epilepsy (FLE). Still, little is known about the structural or functional correlates of such impairments. Particularly, material specificity of functional changes in cerebral activity during memory encoding in FLE is unclear., Methods: We compared 24 FLE patients (15 right-sided) undergoing presurgical evaluation with 30 healthy controls on a memory fMRI-paradigm of learning scenes, faces, and words followed by an out-of-scanner recognition task as well as regarding their mesial temporal lobe (mTL) volumes. We also addressed effects of FLE lateralization and performance level (normal vs. low)., Results: FLE patients had poorer memory performance and larger left hippocampal volumes than controls. Volume increase seemed, however, irrelevant or even dysfunctional for memory performance. Further, functional changes in FLE patients were right-sided for scenes and faces and bilateral for words. In detail, during face encoding, FLE patients had, regardless of their performance level, decreased mTL activation, while during scene and word encoding only low performing FLE patients had decreased mTL along with decreased FL activation. Intact verbal memory performance was associated with higher right frontal activation in FLE patients but not in controls., Significance: Pharmacoresistant FLE has a distinct functional and structural impact on the mTL. Effects vary with the encoded material and patients' performance levels. Thus, in addition to the direct effect of the FL, memory impairment in FLE is presumably to a large part due to functional mTL changes triggered by disrupted FL networks., Plain Language Summary: Frontal lobe epilepsy (FLE) patients may suffer from memory impairment. Therefore, we asked patients to perform a memory task while their brain was scanned by MRI in order to investigate possible changes in brain activation during learning. FLE patients showed changes in brain activation during learning and also structural changes in the mesial temporal lobe, which is a brain region especially relevant for learning but not the origin of the seizures in FLE. We conclude that FLE leads to widespread changes that contribute to FLE patients' memory impairment., (© 2023 The Authors. Epilepsia Open published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.)

Objective: Tau pathology is recognized as a primary contributor to neurodegeneration and clinical symptoms in Alzheimer's disease (AD). This study aims to localize the early tau pathology in cognitively normal older people that is predictive of subsequent neurodegeneration and memory decline, and delineate factors underlying tau-related memory decline in individuals with and without β-amyloid (Aβ)., Methods: A total of 138 cognitively normal older individuals from the Berkeley Aging Cohort Study underwent 11 C-Pittsburgh Compound-B (PiB) positron emission tomography (PET) to determine Aβ positivity and 18 F-Flortaucipir (FTP) PET to measure tau deposition, with prospective cognitive assessments and structural magnetic resonance imaging. Voxel-wise FTP analyses examined associations between baseline tau deposition and longitudinal memory decline, longitudinal hippocampal atrophy, and longitudinal cortical thinning in AD signature regions. We also examined whether hippocampal atrophy and cortical thinning mediate tau effects on future memory decline., Results: We found Aβ-dependent tau associations with memory decline in the entorhinal and temporoparietal regions, Aβ-independent tau associations with hippocampal atrophy within the medial temporal lobe (MTL), and that widespread tau was associated with mean cortical thinning in AD signature regions. Tau-related memory decline was mediated by hippocampal atrophy in Aβ- individuals and by mean cortical thinning in Aβ+ individuals., Interpretation: Our results suggest that tau may affect memory through different mechanisms in normal aging and AD. Early tau deposition independent of Aβ predicts subsequent hippocampal atrophy that may lead to memory deficits in normal older individuals, whereas elevated cortical tau deposition is associated with cortical thinning that may lead to more severe memory decline in AD. ANN NEUROL 2024;95:249-259., (© 2023 American Neurological Association.)

Background: Apolipoproteins and cortical morphology are closely associated with memory complaints, and both may contribute to the development of Alzheimer's disease., Objective: To examine whether apolipoprotein B (ApoB), apolipoprotein A-1 (ApoA1), and their ratio (ApoB/ApoA1) are associated with cortical morphology in patients with memory complaints., Methods: Ninety-seven patients underwent neuropsychological testing, measurements of ApoB, ApoA1, ApoB/ApoA1, plasma Alzheimer's biomarker, apolipoprotein E (ApoE) genotyping, and 3T structural magnetic resonance imaging (sMRI) scans. Based on sMRI scanning locations, patients were categorized into the University of Electronic Science and Technology (UESTC) and the Fourth People's Hospital of Chengdu (FPHC). The Computational Anatomy Toolbox within Statistical Parametric Mapping was used to calculate each patient's cortical morphology index based on sMRI data. The cortical morphology index and apolipoproteins were also analyzed., Results: Significant positive correlations were found between ApoB and sulcal depth in the lateral occipital cortex among the UESTC, the FPHC, and the total sample groups, and negative correlations were observed between sulcal depth in the lateral occipital cortex and the scores of the Shape Trails Test Part A and B. In the FPHC group, the scores of the Montreal Cognitive Assessment Basic, delayed recall of the Auditory Verbal Learning Test, Animal Fluency Test and Boston Naming Test were positively correlated with the sulcal depth., Conclusions: ApoB is associated with the sulcal depth in the lateral occipital cortex, potentially relating to speed/executive function in individuals with memory complaints.

Background: Increasing evidence is demonstrating that degeneration of specific thalamic nuclei, in addition to the hippocampus, may occur in Alzheimer's disease (AD) from the prodromal stage (mild cognitive impairment - MCI) and contribute to memory impairment., Objective: Here, we evaluated the presence of macro and micro structural alterations at the level of the anterior thalamic nuclei (ATN) and medio-dorsal thalamic nuclei (MDTN) in AD and amnestic MCI (aMCI) and the possible relationship between such changes and the severity of memory impairment., Methods: For this purpose, a sample of 50 patients with aMCI, 50 with AD, and 50 age- and education-matched healthy controls (HC) were submitted to a 3-T MRI protocol with whole-brain T1-weighted and diffusion tensor imaging and a comprehensive neuropsychological assessment., Results: At macro-structural level, both the ATN and MDTN were found significantly smaller in patients with aMCI and AD when compared to HC subjects. At micro-structural level, instead, diffusion alterations that significantly differentiated aMCI and AD patients from HC subjects were found only in the ATN, but not in the MDTN. Moreover, diffusion values of the ATN were significantly associated with poor episodic memory in the overall patients' group., Conclusions: These findings represent the first in vivo evidence of a relevant involvement of ATN in the AD-related neurodegeneration and memory profile and strengthen the importance to look beyond the hippocampus when considering neurological conditions characterized by memory decline.

Background: Amyloid positron emission tomography (PET) scans provide in vivo evidence of Alzheimer's disease (AD); however, their high cost limits their use in standard clinical care. Event related potentials (ERPs) may represent an inexpensive and non-invasive additional method for detecting AD pathology., Objective: We investigated whether ERPs, along with neuropsychological data, serve as predictors of amyloid PET status in patients with memory complaints., Methods: Veterans aged 50-100 were recruited from a memory disorders clinic. Participants underwent a neuropsychological battery and an ERP auditory oddball protocol. Twenty-eight patients had a positive amyloid PET scan, and thirty-nine patients had a negative scan., Results: ERP-P200 target amplitude and P200 standard latency were predictors of amyloid PET status. When submitting to ROC analysis, P200 standard latency exhibited the highest specificity and sensitivity in predicting amyloid PET positivity, correctly classifying the amyloid PET status for 86% of patients., Conclusions: ERP-P200 measures are strong indicators of amyloid-β presence in patients from a memory disorder clinic. Increased P200 amplitude and decreased P200 latency in patients with a positive amyloid PET scan may be attributed to hyperactivation of perceptual bottom-up processes compensating for AD-related synaptic loss in the fronto-parietal networks.

Objective: Predicting memory morbidity after temporal lobectomy in patients with temporal lobe epilepsy (TLE) relies on indices of preoperative temporal lobe structural and functional integrity. However, epilepsy is increasingly considered a network disorder, and memory a network phenomenon. We assessed the utility of functional network measures to predict postoperative memory changes., Methods: Seventy-two adults with TLE (37 left/35 right) underwent preoperative resting-state functional magnetic resonance imaging and pre- and postoperative neuropsychological assessment. We compared functional connectivity throughout the memory network of each patient to a healthy control template (n = 19) to identify differences in global organization. A second metric indicated the degree of integration of the to-be-resected temporal lobe with the rest of the memory network. We included these measures in a linear regression model alongside standard clinical variables as predictors of memory change after surgery., Results: Left TLE patients with more atypical memory networks, and with greater functional integration of the to-be-resected region with the rest of the memory network preoperatively, experienced the greatest decline in verbal memory after surgery. Together, these two measures explained 44% of variance in verbal memory change, outperforming standard clinical and demographic variables. None of the variables examined was associated with visuospatial memory change in patients with right TLE., Significance: Resting-state connectivity provides valuable information concerning both the integrity of to-be-resected tissue and functional reserve across memory-relevant regions outside of the to-be-resected tissue. Intrinsic functional connectivity has the potential to be useful for clinical decision-making regarding memory outcomes in left TLE, and more work is needed to identify the factors responsible for differences seen in right TLE., (© 2023 International League Against Epilepsy.)

The chronic intake of 3,4-methylenedioxymethamphetamine (MDMA, "ecstasy") bears a strong risk for sustained declarative memory impairments. Although such memory deficits have been repeatedly reported, their neurofunctional origin remains elusive. Therefore, we here investigate the neuronal basis of altered declarative memory in recurrent MDMA users at the level of brain connectivity. We examined a group of 44 chronic MDMA users and 41 demographically matched controls. Declarative memory performance was assessed by the Rey Auditory Verbal Learning Test and a visual associative learning test. To uncover alterations in the whole brain connectome between groups, we employed a data-driven multi-voxel pattern analysis (MVPA) approach on participants' resting-state functional magnetic resonance imaging data. Recent MDMA use was confirmed by hair analyses. MDMA users showed lower performance in delayed recall across tasks compared to well-matched controls with moderate-to-strong effect sizes. MVPA revealed a large cluster located in the left postcentral gyrus of global connectivity differences between groups. Post hoc seed-based connectivity analyses with this cluster unraveled hypoconnectivity to temporal areas belonging to the auditory network and hyperconnectivity to dorsal parietal regions belonging to the dorsal attention network in MDMA users. Seed-based connectivity strength was associated with verbal memory performance in the whole sample as well as with MDMA intake patterns in the user group. Our findings suggest that functional underpinnings of MDMA-related memory impairments encompass altered patterns of multimodal sensory integration within auditory processing regions to a functional heteromodal connector hub, the left postcentral gyrus. In addition, hyperconnectivity in regions of a cognitive control network might indicate compensation for degraded sensory processing., (© 2023 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.)

Background and Objectives: The predictable Braak staging scheme suggests that cortical tau progression may be related to synaptically connected neurons. Animal and human neuroimaging studies demonstrated that changes in neuronal activity contribute to tau spreading. Whether similar mechanisms explain tau progression from the locus coeruleus (LC), a tiny noradrenergic brainstem nucleus involved in novelty, learning, and memory and among the earliest regions to accumulate tau, has not yet been established. We aimed to investigate whether novelty-related LC activity was associated with the accumulation of cortical tau and its implications for cognitive decline., Methods: We combined functional MRI data of a novel vs repeated face-name learning paradigm, [ 18 F]-FTP-PET, [ 11 C]-PiB-PET, and longitudinal cognitive data from 92 well-characterized older individuals in the Harvard Aging Brain Study. We related novelty vs repetition LC activity to cortical tau deposition and to longitudinal decline in memory, executive function, and the Preclinical Alzheimer Disease Cognitive Composite (version 5; PACC5). Structural equation modeling was used to examine whether entorhinal cortical (EC) tau mediated the relationship between LC activity and cognitive decline and whether this depended on beta-amyloid deposition., Results: The participants' average age at baseline was 69.67 ± 10.14 years. Fifty-one participants were female. Ninety-one participants were cognitively normal (CDR global = 0), and one participant had mild cognitive impairment (CDR global = 0.5) at baseline. Lower novelty-related LC activity was specifically related to greater tau deposition in the medial-lateral temporal cortex and steeper memory decline. LC activity during novelty vs repetition was not related to executive dysfunction or decline on the PACC5. The relationship between LC activity and memory decline was partially mediated by EC tau, particularly in individuals with elevated beta-amyloid deposition., Discussion: Our results suggested that lower novelty-related LC activity is associated with the emergence of EC tau and that the downstream effects of this LC-EC pathway on memory decline also require the presence of elevated beta-amyloid. Longitudinal studies are required to investigate whether optimal LC activity has the potential to delay tau spread and memory decline, which may have implications for designing targeted interventions promoting resilience., (© 2023 American Academy of Neurology.)

Aims: To compare different patterns of memory impairment in patients with two subtypes of mesial temporal lobe epilepsy (MTLE) and healthy controls., Methods: Thirty-five healthy controls and 41 patients with MTLE were recruited, of which 25 patients were diagnosed as hippocampal sclerosis (HS-MTLE), and the rest 16 patients were lesion-negative (MRI-neg MTLE). Participants completed the Wechsler memory assessment and a short-term memory game on an automated computer-based memory assessment platform with an eye tracker., Results: Both the MRI-neg MTLE and HS-MTLE groups took longer time to complete the short-term memory game than healthy controls (p < 0.001, Cohen's d = 1.087; p = 0.047, Cohen's d = 0.787). During the memory encoding phase, the MRI-neg MTLE group spent significantly shorter time than healthy controls on the difficult levels with three (p = 0.004, Cohen's d = 0.993) and four targets (p = 0.016, Cohen's d = 0.858). During the memory decoding phase, the HS-MTLE group spent less time looking on the targets compared to controls when recalling and finding four targets (p = 0.004, Cohen's d = -0.793), while the MRI-neg MTLE group spent significantly longer time on the distractors and shorter time on the region of interests (ROIs) for all difficulty levels (all p < 0.05) than controls. Furthermore, the eye tracking data were correlated with the scores of the Wechsler Memory Scale after Bonferroni correction (p < 0.05)., Conclusion: Patients with MRI-neg MTLE demonstrate impaired memory mostly due to attention deficits, while those with HS-MTLE show memory impairment with relative sparing of attention. Eye tracking technology has the potential of facilitating the investigation of the mechanism of memory defect in MTLE and can serve as a supplementary neuropsychological tool for clinical diagnosis and long-term monitoring., (© 2023 The Authors. CNS Neuroscience & Therapeutics published by John Wiley & Sons Ltd.)

Introduction: Resting-state functional magnetic resonance imaging (fMRI) graph theory may help detect subtle functional connectivity changes affecting memory prior to impairment., Methods: Cognitively normal apolipoprotein E (APOE) ε4 carriers/noncarriers underwent longitudinal cognitive assessment and one-time MRI. The relationship of left/right hippocampal connectivity and memory trajectory were compared between carriers/noncarriers., Results: Steepness of verbal memory decline correlated with decreased connectivity in the left hippocampus, only among APOE ε4 carriers. Right hippocampal metrics were not correlated with memory and there were no significant correlations in the noncarriers. Verbal memory decline correlated with left hippocampal volume loss for both carriers and noncarriers, with no other significant volumetric findings., Discussion: Findings support early hippocampal dysfunction in intact carriers, the AD disconnection hypothesis, and left hippocampal dysfunction earlier than the right. Combining lateralized graph theoretical metrics with a sensitive measure of memory trajectory allowed for detection of early-stage changes in APOE ε4 carriers before symptoms of mild cognitive impairment are present., Highlights: Graph theory connectivity detects preclinical hippocampal changes in APOE ε4 carriers. The AD disconnection hypothesis was supported in unimpaired APOE ε4 carriers. Hippocampal dysfunction starts asymmetrically on the left., (© 2023 the Alzheimer's Association.)

Older adults may harbor large amounts of amyloid-β (Aβ) pathology, yet still perform at age-normal levels on memory assessments. We tested whether functional brain networks confer resilience or compensatory mechanisms to support memory in the face of Aβ pathology. Sixty-five cognitively normal older adults received high-resolution resting state fMRI to assess functional networks, 18F-florbetapir-PET to measure Aβ, and a memory assessment. We characterized functional networks with graph metrics of local efficiency (information transfer), modularity (specialization of functional modules), and small worldness (balance of integration and segregation). There was no difference in functional network measures between older adults with high Aβ (Aβ+) compared to those with no/low Aβ (Aβ-). However, in Aβ+ older adults, increased local efficiency, modularity, and small worldness were associated with better memory performance, while this relationship did not occur Aβ- older adults. Further, the association between increased local efficiency and better memory performance in Aβ+ older adults was localized to local efficiency of the default mode network and hippocampus, regions vulnerable to Aβ and involved in memory processing. Our results suggest functional networks with modular and efficient structures are associated with resilience to Aβ pathology, providing a functional target for intervention., (© 2023. Springer Nature Limited.)

Background and Objectives: Neuropsychological research on mesial temporal lobe epilepsy (MTLE) often highlights material-specific memory deficits, but a lesion-focused model may not accurately reflect the underlying networks that support episodic memory in these patients. Our study evaluated the pathophysiology behind verbal learning/memory deficits as revealed by hypometabolism quantified through 18-fluorodeoxyglucose positron emission tomography (FDG-PET)., Methods: This retrospective study included thirty presurgical patients with intractable unilateral MTLE who underwent interictal FDG-PET and verbal memory assessment (12 females, mean age: 38.73 years). Fluorodeoxyglucose-positron emission tomography mapping was performed with voxel-based mapping of glucose utilization to a database of age-matched controls to derive regional Z-scores. Neuropsychological outcome variables included scores on learning and recall trials of two distinct verbal memory measures validated for use in epilepsy research. Pearson's correlations evaluated relationships between clinical variables and verbal memory. Linear regression was used to relate regional hypometabolism and verbal memory assessment. Post hoc analyses assessed areas of FDG-PET hypometabolism (threshold Z ≤ -1.645 below mean) where verbal memory was impaired., Results: Verbal memory deficits correlated with hypometabolism in limbic structures ipsilateral to language dominance but also correlated with hypometabolism in networks involving the ipsilateral perisylvian cortex and contralateral limbic and nonlimbic structures., Discussion: We conclude that traditional models of verbal memory may not adequately capture cognitive deficits in a broader sample of patients with MTLE. This study has important implications for epilepsy surgery protocols that use neuropsychological data and FDG-PET to draw conclusions about surgical risks., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Older adults with Type II Diabetes Mellitus (DM) experience mild cognitive impairment, specifically in the domain of recall/working memory. No consistent causative structural cortical deficits have been identified in persons with DM (PwDM). Memory deficits may be exacerbated in older adult females, who are at the highest risk of cardiovascular decline due to DM. The focus of the current study was to evaluate functional cortical hemodynamic activity during memory tasks in postmenopausal PwDM. Functional Near Infrared Spectroscopy (fNIRS) was used to monitor oxyhemoglobin (HbO) and deoxyhemoglobin (HbR) during memory-based tasks in a cross-sectional sample of postmenopausal women with DM. Twenty-one community-dwelling DM females (age = 65 ± 6 years) and twenty-one age- and sex-matched healthy controls (age = 66 ± 6 years) were evaluated. Working memory performance (via N-back) was evaluated while study participants donned cortical fNIRS. Health state, metabolic data, and menopausal status data were also collected. Deficits in working memory accuracy were found in the DM group as compared to controls. Differences in HbO responses emerged in the DM group. The DM group exhibited altered PFC activity magnitudes and increased functional cortical activity across ROIs compared to controls. HbO and HbR responses were not associated with worsened health state measures. These data indicate a shift in cortical activity patterns with memory deficits in postmenopausal PwDM. This DM-specific shift of HbO is a novel finding that is unlikely to be detected by fMRI. This underscores the value of using non-MRI-based neuroimaging techniques to evaluate cortical hemodynamic function to detect early mild cognitive impairment., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: Risk for memory decline is a common concern for individuals with temporal lobe epilepsy (TLE) undergoing surgery. Global and local network abnormalities are well documented in TLE. However, it is less known whether network abnormalities predict postsurgical memory decline. The authors examined the role of preoperative global and local white matter network organization and risk of postoperative memory decline in TLE., Methods: One hundred one individuals with TLE (n = 51 with left TLE and 50 with right TLE) underwent preoperative T1-weighted MRI, diffusion MRI, and neuropsychological memory testing in a prospective longitudinal study. Fifty-six age- and sex-matched controls completed the same protocol. Forty-four patients (22 with left TLE and 22 with right TLE) subsequently underwent temporal lobe surgery and postoperative memory testing. Preoperative structural connectomes were generated via diffusion tractography and analyzed using measures of global and local (i.e., medial temporal lobe [MTL]) network organization. Global metrics measured network integration and specialization. The local metric was calculated as an asymmetry of the mean local efficiency between the ipsilateral and contralateral MTLs (i.e., MTL network asymmetry)., Results: Higher preoperative global network integration and specialization were associated with higher preoperative verbal memory function in patients with left TLE. Higher preoperative global network integration and specialization, as well as greater leftward MTL network asymmetry, predicted greater postoperative verbal memory decline for patients with left TLE. No significant effects were observed in right TLE. Accounting for preoperative memory score and hippocampal volume asymmetry, MTL network asymmetry uniquely explained 25%-33% of the variance in verbal memory decline for left TLE and outperformed hippocampal volume asymmetry and global network metrics. MTL network asymmetry alone produced good diagnostic classification of memory decline in left TLE (i.e., an area under the receiver operating characteristic curve of 0.80-0.84 and correct classification of 65%-76% of cases with cross-validation)., Conclusions: These preliminary data suggest that global white matter network disruption contributes to verbal memory impairment preoperatively and predicts postsurgical verbal memory outcomes in left TLE. However, a leftward asymmetry of MTL white matter network organization may confer the highest risk for verbal memory decline. Although this requires replication in a larger sample, the authors demonstrate the importance of characterizing preoperative local white matter network properties within the to-be-operated hemisphere and the reserve capacity of the contralateral MTL network, which may eventually be useful in presurgical planning.

Episodic memory deficits occur in people living with HIV (PLWH) and individuals with Parkinson's disease (PD). Given known effects of HIV and PD on frontolimbic systems, episodic memory deficits are often attributed to executive dysfunction. Although executive dysfunction, evidenced as retrieval deficits, is relevant to mnemonic deficits, learning deficits may also contribute. Here, the California Verbal Learning Test-II, administered to 42 PLWH, 41 PD participants, and 37 controls, assessed learning and retrieval using measures of free recall, cued recall, and recognition. Executive function was assessed with a composite score comprising Stroop Color-Word Reading and Backward Digit Spans. Neurostructural correlates were examined with MRI of frontal (precentral, superior, orbital, middle, inferior, supplemental motor, medial) and limbic (hippocampus, thalamus) volumes. HIV and PD groups were impaired relative to controls on learning and free and cued recall trials but did not differ on recognition or retention of learned material. In no case did executive functioning solely account for the observed mnemonic deficits or brain-performance relations. Critically, the shared learning and retrieval deficits in HIV and PD were related to different substrates of frontolimbic mnemonic neurocircuitry. Specifically, diminished learning and poorer free and cued recall were related to smaller orbitofrontal volume in PLWH but not PD, whereas diminished learning in PD but not PLWH was related to smaller frontal superior volume. In PD, poorer recognition correlated with smaller thalamic volume and poorer retention to hippocampal volume. Although memory deficits were similar, the neural correlates in HIV and PD suggest different pathogenic mechanisms., (© 2023. The Author(s).)

Background: Previous studies have demonstrated structural and functional changes of the hippocampus in patients with major depressive disorder (MDD). However, no studies have analyzed the dynamic functional connectivity (dFC) of hippocampal subregions in melancholic MDD. We aimed to reveal the patterns for dFC variability in hippocampus subregions - including the bilateral rostral and caudal areas and its associations with cognitive impairment in melancholic MDD., Methods: Forty-two treatment-naive MDD patients with melancholic features and 55 demographically matched healthy controls were included. The sliding-window analysis was used to evaluate whole-brain dFC for each hippocampal subregions seed. We assessed between-group differences in the dFC variability values of each hippocampal subregion in the whole brain and cognitive performance on the MATRICS Consensus Cognitive Battery (MCCB). Finally, association analysis was conducted to investigate their relationships., Results: Patients with melancholic MDD showed decreased dFC variability between the left rostral hippocampus and left anterior lobe of cerebellum compared with healthy controls (voxel p < 0.005, cluster p < 0.0125, GRF corrected), and poorer cognitive scores in working memory, verbal learning, visual learning, and social cognition (all p < 0.05). Association analysis showed that working memory was positively correlated with the dFC variability values of the left rostral hippocampus-left anterior lobe of the cerebellum ( r = 0.338, p = 0.029) in melancholic MDD., Conclusions: These findings confirmed the distinct dynamic functional pathway of hippocampal subregions in patients with melancholic MDD, and suggested that the dysfunction of hippocampus-cerebellum connectivity may be underlying the neural substrate of working memory impairment in melancholic MDD.

Background: Left-predominant neurodegeneration of the anterior temporal lobe (ATL) and the associated syndrome termed semantic variant primary progressive aphasia (svPPA) are well characterized. Less is known about right-predominant neurodegeneration of the ATL, which has been associated with the clinical syndrome named right temporal variant of frontotemporal dementia (rtvFTD). Here, we assessed glucose metabolism across the brain, cognitive performance, and mortality in patients with right-predominant neurodegeneration of the ATL., Methods: Patients with predominant hypometabolism of the ATL on FDG PET (as a measure of neurodegeneration) were retrospectively identified and categorized into those with asymmetrical right, left, or symmetric bilateral involvement (N = 10, 17, and 8). We compared whole-brain, normalized regional glucose metabolism using SPM12, cognitive performance on the CERAD Neuropsychological Assessment Battery, and mortality risk (age- and sex-adjusted Cox proportional hazard model) between groups., Results: Hypometabolism was most pronounced and extensive in patients with right-predominant neurodegeneration of the ATL. Beyond the right temporal lobe, right frontal and left temporal lobes were affected in these patients. Cognitive performance was similarly impaired in all three groups, with predominant naming and hippocampal-dependent memory deficits. Mortality risk was 6.1 times higher in patients with right- than left-predominant ATL neurodegeneration (p < 0.05). Median survival duration after PET was shortest in patients with right- and longest in patients with left-predominant ATL neurodegeneration (5.7 vs 8.3 years after examination)., Discussion: More extensive neurodegeneration and shorter survival duration in patients with right- than left-predominant neurodegeneration of the ATL might indicate that the former consult memory clinics at a later disease stage, when symptoms like naming and episodic memory deficits have already emerged. At the time of diagnosis, the shorter survival duration of patients with right- than left-predominant ATL neurodegeneration should be kept in mind when counseling patients and caregivers., (© 2023. The Author(s).)

Introduction: The hippocampus is the most prominent single region of interest (ROI) for the diagnosis and prediction of Alzheimer's disease (AD). However, its suitability in the earliest stages of cognitive decline, i.e., subjective cognitive decline (SCD), remains uncertain which warrants the pursuit of alternative or complementary regions. The amygdala might be a promising candidate, given its implication in memory as well as other psychiatric disorders, e.g. depression and anxiety, which are prevalent in SCD. In this 7 tesla (T) magnetic resonance imaging (MRI) study, we aimed to compare the contribution of volumetric measurements of the hippocampus, the amygdala, and their respective subfields, for early diagnosis and prediction in an AD-related study population., Methods: Participants from a longitudinal study were grouped into SCD (n = 29), mild cognitive impairment (MCI, n = 23), AD (n = 22) and healthy control (HC, n = 31). All participants underwent 7T MRI at baseline and extensive neuropsychological testing at up to three visits (baseline n = 105, 1-year n = 78, 3-year n = 39). Analysis of covariance (ANCOVA) was used to assess group differences of baseline volumes of the amygdala and the hippocampus and their subfields. Linear mixed models were used to estimate the effects of baseline volumes on yearly changes of a z-scaled memory score. All models were adjusted to age, sex and education., Results: Compared to the HC group, individuals with SCD showed smaller amygdala ROI volumes (range across subfields -11% to -1%), but not hippocampus ROI volumes (-2% to 1%) except for the hippocampus-amygdala-transition-area (-7%). However, cross-sectional associations between baseline memory and volumes were smaller for amygdala ROIs (std. ß [95% CI] ranging between 0.16 [0.08; 0.25] and 0.46 [0.31; 0.60]) than hippocampus ROIs (between 0.32 [0.19; 0.44] and 0.53 [0.40; 0.67]). Further, the association of baseline volumes with yearly memory change in the HC and SCD groups was similarly weak for amygdala ROIs and hippocampus ROIs. In the MCI group, volumes of amygdala ROIs were associated with a relevant yearly memory decline [95% CI] ranging between -0.12 [-0.24; 0.00] and -0.26 [-0.42; -0.09] for individuals with 20% smaller volumes than the HC group. However, effects were stronger for hippocampus ROIs with a corresponding yearly memory decline ranging between -0.21 [-0.35; -0.07] and -0.31 [-0.50; -0.13]., Conclusion: Volumes of amygdala ROIs, as determined by 7T MRI, might contribute to objectively and non-invasively identify patients with SCD, and thus aid early diagnosis and treatment of individuals at risk to develop dementia due to AD, however associations with other psychiatric disorders should be evaluated in further studies. The amygdala's value in the prediction of longitudinal memory changes in the SCD group remains questionable. Primarily in patients with MCI, memory decline over 3 years appears to be more strongly associated with volumes of hippocampus ROIs than amygdala ROIs., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

White matter hyperintensities are a marker of small vessel cerebrovascular disease that are strongly related to cognition in older adults. Similarly, medial temporal lobe atrophy is well-documented in aging and Alzheimer's disease and is associated with memory decline. Here, we assessed the relationship between lobar white matter hyperintensities, medial temporal lobe subregional volumes, and hippocampal memory in older adults. We collected MRI scans in a sample of 139 older adults without dementia (88 females, mean age (SD) = 76.95 (10.61)). Participants were administered the Rey Auditory Verbal Learning Test (RAVLT). Regression analyses tested for associations among medial temporal lobe subregional volumes, regional white matter hyperintensities and memory, while adjusting for age, sex, and education and correcting for multiple comparisons. Increased occipital white matter hyperintensities were related to worse RAVLT delayed recall performance, and to reduced CA1, dentate gyrus, perirhinal cortex (Brodmann area 36), and parahippocampal cortex volumes. These medial temporal lobe subregional volumes were related to delayed recall performance. The association of occipital white matter hyperintensities with delayed recall performance was fully mediated statistically only by perirhinal cortex volume. These results suggest that white matter hyperintensities may be associated with memory decline through their impact on medial temporal lobe atrophy. These findings provide new insights into the role of vascular pathologies in memory loss in older adults and suggest that future studies should further examine the neural mechanisms of these relationships in longitudinal samples., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022. Published by Elsevier Inc.)

The perforant path, the white matter bundle connecting the entorhinal cortex (ERC) with the hippocampal formation deteriorates with age-related cognitive decline. Previous investigations using diffusion-weighted MRI to quantify perforant path integrity in-vivo have been limited due to image resolution or have quantified the perforant path using methods susceptible to partial volume effects such as the tensor model and without consideration of its 3-dimensional morphology. In this investigation, we use quantitative-anisotropy informed tractography derived from ultra-high resolution diffusion imaging (ZOOMit) to investigate structural connectivity of the perforant path and other medial temporal lobe (MTL) pathways in older adults (63 to 98 years old, n = 51). We show that graph density within the MTL declines with age and is associated with lower delayed recall performance. We also show that older age and poorer delayed recall are associated with reduced streamlines connecting the ERC and dentate gyrus of the hippocampus (the putative perforant path). This work suggest that intra-MTL connectivity may new candidate biomarkers for age-related cognitive decline., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Heterogeneity has been a persistent challenge in understanding Schizophrenia Spectrum Disorders (SSD). Traditional case-control comparisons often show variable results, and may not map well onto individuals. To better understand heterogeneity and group differences in SSD compared to typically developing controls (TDC), we examined variability in functional brain activity during a working memory (WM) task with known deficits in SSD. Neuroimaging and behavioural data were extracted from two datasets collectively providing 34 TDC and 56 individuals with SSD (n = 90). Functional activity in response to an N-Back WM task (3-Back vs 1-Back) was examined between and within groups. Individual variability was calculated via the correlational distance of fMRI activity maps between participants; mean correlational distance from one participant to all others was defined as a 'variability score'. Greater individual variability in functional activity was found in SSD compared to TDC (p = 0.00090). At the group level, a case-control comparison suggested SSD had reduced activity in task positive and task negative networks. However, when SSD were divided into high and low variability subgroups, the low variability groups showed no differences relative to TDC while the high variability group showed little activity at the group level. Our results imply prior case-control differences may be driven by a subgroup of SSD who do not show specific impairments but instead show more 'idiosyncratic' activity patterns. In SSD but not TDC, variability was also related to cognitive performance and age. This novel approach focusing on individual variability has important implications for understanding the neurobiology of SSD., Competing Interests: Declaration of competing interest The authors have no conflicts of interest., (Copyright © 2022. Published by Elsevier B.V.)

Background: Adults with Down syndrome are at an ultra-high risk of developing early-onset Alzheimer's disease. Episodic memory deficits are one of the earliest signs of the disease, but their association with regional brain atrophy in the population with Down syndrome has not been explored. We aimed to investigate the neuroanatomical correlates of episodic memory in adults with Down syndrome and symptomatic Alzheimer's disease., Methods: Single-center, cross-sectional study. A total of 139 adults with Down syndrome (85 asymptomatic and 54 with symptomatic Alzheimer's disease) were included in the study (mean age 43.6 ± 10.9 years, 46% female). Episodic memory was assessed using the modified Cued Recall Test. Immediate (trial 1 free immediate recall, trial 3 free immediate recall, total free immediate recall score, and total immediate score) and delayed scores (free delayed recall score and total delayed score) were examined. Cortical thickness from magnetic resonance imaging was determined with surface-based morphometry using the FreeSurfer 6.0 software package. The clusters of reduced cortical thickness were compared between symptomatic and asymptomatic participants to create a cortical atrophy map. Then, the correlation between cortical thickness and the modified Cued Recall Test subscores were separately assessed in symptomatic and asymptomatic subjects, controlling for age, sex, and severity of intellectual disability., Results: Compared with asymptomatic participants, those with symptomatic Alzheimer's disease showed a pattern of cortical atrophy in posterior parieto-temporo-occipital cortices. In symptomatic subjects, trial 1 immediate free recall significantly correlated with cortical atrophy in lateral prefrontal regions. Trial 3 free immediate recall and total free immediate recall were associated with the most widespread cortical atrophy. Total immediate score was related to posterior cortical atrophy, including lateral parietal and temporal cortex, posterior cingulate cortex, precuneus, and medial temporal lobe areas. Delayed memory scores were associated with cortical atrophy in temporoparietal and medial temporal lobe regions. No significant relationships were observed between episodic memory measures and cortical atrophy in asymptomatic subjects., Conclusions: Different episodic memory measures were associated with cortical atrophy in specific brain regions in adults with Down syndrome and Alzheimer's disease. These results overlap with those described in sporadic Alzheimer's disease and further support the similarities between Down syndrome-associated Alzheimer's disease and that in the general population., (© 2022. The Author(s).)

Episodic memory ability relies on hippocampal-prefrontal connectivity. However, few studies have examined relationships between memory performance and white matter (WM) microstructure in hippocampal-prefrontal pathways in schizophrenia-spectrum disorder (SSDs). Here, we investigated these relationships in individuals with first-episode psychosis (FEP) and chronic schizophrenia-spectrum disorders (SSDs) using tractography analysis designed to interrogate the microstructure of WM tracts in the hippocampal-prefrontal pathway. Measures of WM microstructure (fractional anisotropy [FA], radial diffusivity [RD], and axial diffusivity [AD]) were obtained for 47 individuals with chronic SSDs, 28 FEP individuals, 52 older healthy controls, and 27 younger healthy controls. Tractography analysis was performed between the hippocampus and three targets involved in hippocampal-prefrontal connectivity (thalamus, amygdala, nucleus accumbens). Measures of WM microstructure were then examined in relation to episodic memory performance separately across each group. Both those with FEP and chronic SSDs demonstrated impaired episodic memory performance. However, abnormal WM microstructure was only observed in individuals with chronic SSDs. Abnormal WM microstructure in the hippocampal-thalamic pathway in the right hemisphere was associated with poorer memory performance in individuals with chronic SSDs. These findings suggest that disruptions in WM microstructure in the hippocampal-prefrontal pathway may contribute to memory impairments in individuals with chronic SSDs but not FEP., (© 2021. Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Episodic memory impairment may occur in progressive supranuclear palsy (PSP). However, it remains uncertain whether this is due to executive dysfunction or to the involvement of brain areas responsible for memory., Objectives: To investigate the specific brain regions underlying episodic memory impairment in PSP., Methods: Twenty-one patients with PSP and 20 healthy controls underwent the Figure Memory Test (FMT) from the Brief Cognitive Screening Battery and brain MRI. We explored correlations between gray matter volumes and memory scores in PSP patients, adjusting for age and performance on the Frontal Assessment Battery., Results: PSP patients performed worse than controls (p < 0.001) on delayed recall in the FMT. Delayed recall scores correlated to bilateral hippocampal and parahippocampal volumes in PSP patients., Conclusions: Medial temporal structures may play a role in episodic memory impairment in PSP, suggesting that amnesia in PSP is not solely due to executive dysfunction., (© 2022. Fondazione Società Italiana di Neurologia.)

Background: Patients with postacute anti-N-methyl-D-aspartate (anti-NMDA) receptor encephalitis are often left with permanent memory impairments. Given that NMDA receptors are essential to memory encoding, and encoding processes have been suggested to contribute to the success of memory retrieval, we investigate whether postacute anti-NMDA receptor encephalitis leads to abnormal brain activation during verbal memory encoding and its potential effects on subsequent memory retrieval performance. Methods: To address this issue, this study recruited 21 adult patients with anti-NMDA receptor encephalitis past the acute stage and 22 healthy controls (HCs). Functional magnetic resonance imaging (fMRI) data were collected when they completed an episodic memory task. Results: At the neural level, the patients showed higher brain activation than the HCs in the bilateral hippocampus/parahippocampus (HG/PHG), right superior temporal gyrus (STG), and right thalamus during memory encoding. At the behavioral level, the patients showed worse memory retrieval performance than the HCs. Importantly, greater brain activation in the left HG/PHG during memory encoding was significantly associated with worse memory retrieval performance among the patients. Conclusion: Our findings indicate that postacute anti-NMDA receptor encephalitis is likely related to altered brain activation during memory encoding. Particularly, less memory retrieval performance often observed in patients with postacute anti-NMDA receptor encephalitis may result from abnormal activation in HG during encoding. These observations may enhance our understanding of NMDA receptor dysfunction in the human brain. Impact statement Patients with anti-N-methyl-D-aspartate (anti-NMDA) receptor encephalitis are often left with permanent memory impairments. In this study, brain activation during verbal memory encoding and its potential effects on subsequent memory retrieval performance are addressed using 21 adult patients with postacute anti-NMDA receptor encephalitis and 22 healthy controls. Greater brain activation in the left hippocampus/parahippocampus during memory encoding was significantly associated with worse memory retrieval performance among the patients. These observations enhance our understanding of NMDA receptor dysfunction in the human brain.

Hippocampal and thalamo-cortico-striatal networks are critical for memory function as well as execution of a variety of learning strategies. In subjects with memory impairment as a sequel of traumatic brain injury (TBI), the contribution of late metabolic depression across these networks to memory deficit is poorly understood. We used [18F]-FDG-PET to measure chronic post-TBI glucose uptake in the striatum and connected brain areas (septal and temporal hippocampus, thalamus, entorhinal cortex, frontoparietal cortex and amygdala) in rats with lateral fluid-percussion injury (LFPI). Then we assessed a link between network hypometabolism and memory impairment. At 4 months post TBI, glucose uptake was decreased in ipsilateral striatum (10%, p = 0.027), frontoparietal cortex (17%, p = 0.00009), and hippocampus (22%, p = 0.027) as compared to sham operated controls. Thalamic uptake was 6% lower ipsilaterally than contralaterally, p = 0.00004). At 5 months, Morris water maze (MWM) showed memory impairment in 83% of the rats with TBI. The lower the hippocampal or striatal [18F]-FDG uptake, the poorer the MWM performance (hippocampus: r = -0.471, p < 0.05; striatum: r = -0.696, p < 0.001). Striatal [18F]-FDG-PET identified the injured animals with memory impairment with 100% specificity and sensitivity (AUC = 1.000, p = 0.009). Interestingly, the low striatal glucose uptake was a better diagnostic biomarker for memory impairment than the reduced hippocampal (AUC = 0.806, p = 0.112) or entorhinal (AUC = 0.528, p = 0.885) glucose uptake. The volumetric atrophy assessed in T2 weighted MRI or the gliotic area in Nissl staining did not correlate with glucose uptake. Arterial spin labeling did not indicate any reduction in the striatal blood flow. Our study suggests that TBI-induced chronic hypometabolism in striatum contributes to the cognitive deficits., (Copyright © 2022 The Author(s). Published by Elsevier B.V. All rights reserved.)

Hippocampal circuitry and related cortical connections are altered in first episode psychosis (FEP) and are associated with verbal memory deficits, as well as positive and negative symptoms. There are robust sex differences in the clinical presentation of psychosis, including poorer verbal memory in male patients. Consideration of sex differences in hippocampal-cortical circuitry and their associations with different behavioral dimensions may be useful for understanding the underlying pathophysiology of verbal memory deficits and related symptomatology in psychosis. Here, we use a data-driven approach to simultaneously capture the complex links between sex, verbal memory, symptoms, and cortical-hippocampal brain metrics in FEP. Structural magnetic resonance imaging and behavioral data were acquired from 100 FEP patients (75 males, 25 females) and 87 controls (55 males, 32 females). Multivariate brain-behavior associations were examined in FEP using partial least squares to map sociodemographic, verbal memory, and clinical data onto brain morphometry. The analysis identified two sex-dependent patterns of verbal memory, symptoms, and brain structure. In male patients, verbal memory deficits and core psychotic symptoms were associated with both increased and decreased frontal and temporal cortical thickness and reductions in CA2/3 hippocampal subfield and fornix volumes. In female patients, fewer negative/depressive symptoms were associated with a more attenuated cortical thickness pattern and more diffuse reductions in hippocampal white matter regions. Taken together, the results contribute towards better understanding the underlying pathophysiology of psychosis by highlighting the unique contribution of specific hippocampal subfields and surrounding white matter and their connections with broader cortical networks in a sex-dependent manner., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background and Purpose: Verbal declarative memory performance relies on frontotemporal connectivity. The uncinate fasciculus is a major association tract connecting the frontal and temporal lobes. Hemispheric asymmetries contribute to various cognitive and neurobehavioral abilities. Here we investigated microstructural alterations and hemispheric asymmetry of the uncinate fasciculus and their possible correlation to memory performance of children with learning disorders attributed to verbal memory deficits., Materials and Methods: Two groups of right-handed children with learning disorders attributed to verbal memory deficits and typically developing children ( n = 20 and 22, respectively) underwent DTI on a 1.5T scanner. Tractography of the uncinate fasciculus in both hemispheres was performed, and fractional anisotropy and diffusivity indices (radial diffusivity, axial diffusivity, and trace) were obtained. The asymmetry index was calculated. Verbal memory was assessed using subsets of the Stanford Binet Intelligence Scale, 4th edition, a dyslexia assessment test, and the Illinois test of Psycholinguistic Abilities. Correlation between diffusion metrics and verbal memory performance was investigated in the learning disorders group. Also, hemispheric differences in each group were tested, and between-group comparisons were performed., Results: Children with learning disorders showed absence of the normal left-greater-than-right asymmetry of fractional anisotropy and the normal right-greater-than-left asymmetry of radial diffusivity seen in typically developing children. Correlation with verbal memory subsets revealed that the higher the fractional anisotropy and asymmetry index, the better the rapid naming performance ( P <.05) was., Conclusions: These findings demonstrated microstructural aberrations with reduction of hemispheric asymmetry of the uncinate fasciculus, which could disrupt the normal frontotemporal connectivity in children with learning disorders attributed to verbal memory deficits. This outcome gives more understanding of pathologic mechanisms underlying this disorder., (© 2022 by American Journal of Neuroradiology.)

Magnetic resonance imaging (MRI) is currently under investigation as a non-invasive tool to monitor neurodevelopmental trajectories and predict risk of cognitive deficits following white matter injury (WMI) in very preterm infants. In the present study, we evaluated the capacity of multimodal MRI (high-resolution T2-weighted imaging and diffusion tensor imaging)to assess changes following WMI and their relationship to learning and memory performance in Wistar rats as it has been demonstrated for preterm infants. Multimodal MRI performed at P31-P32 shown that animals exposed to neonatal LPS could be classified into two groups: minimal and overt injury. Animals with overt injury had significantly enlarged ventricles, hippocampal atrophy, diffusivity changes in hippocampal white and gray matter, in the striatum and the cortex. Following neonatal LPS exposure, animals presented learning and memory impairments as shown at the fear conditioning test at P36-P38. The severity of learning and memory deficits was related to increased mean diffusivity in the hippocampal region. In conclusion, non-invasive multimodal MRI (volumetric and DTI) assessed and classified the extent of injury at long-term following neonatal LPS exposure. Microstructural changes in the hippocampus at DTI were associated to learning and memory impairments. This further highlights the utility of multimodal MRI as a non-invasive quantitative biomarker following perinatal inflammation., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Ageing displays a low-grade pro-inflammatory profile in blood and the brain. Accumulation of pro-inflammatory cytokines, microglia activation and volumetric changes in the brain correlate with cognitive decline in ageing models. However, the interplay between them is not totally understood. Here, we aimed to globally identify an age-dependent pro-inflammatory profile and microglia morphological plasticity that favors major volume changes in the brain associated with cognitive decline. Cluster analysis of behavioral data obtained from 2-,12- and 20-month-old male C57BL/6 mice revealed age-dependent cognitive decline after the Y-maze, Barnes maze, object recognition (NORT) and object location tests (OLT). Global magnetic resonance imageing (MRI) analysis by deformation-based morphometry (DBM) in the brain identified a volume increase in the fornix and a decrease in the left medial entorhinal cortex (MEntC) during ageing. Notably, the fornix shows an increase in the accumulation of pro-inflammatory cytokines, whereas the left MEntC displays a decrease. Morphological assessment of microglia also confirms an active and dystrophic phenotype in the fornix and a surveillance phenotype in the left MEntC. Finally, biological modeling revealed that age-related volume increase in the fornix was associated with dystrophic microglia and cognitive impairment, as evidenced by failure on tasks examining memory of object location and novelty. Our results propose that the morphological plasticity of microglia might contribute to volumetric changes in brain regions associated with cognitive decline during physiological ageing., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interests., (Copyright © 2022. Published by Elsevier Inc.)

Temporal lobe epilepsy (TLE) is a network disorder with a high incidence of memory impairment. Memory processing ability highly depends on the dynamic coordination between distinct modules within the hippocampal network. Here, we investigate the relationship between memory phenotypes and modular alterations of dynamic functional connectivity (FC) in the hippocampal network in TLE patients. Then, 31 healthy controls and 66 TLE patients with hippocampal sclerosis were recruited. The patients were classified into memory-intact (MI, 35 cases) group and memory-deficit (MD, 31 cases) group, each based on individual's Wechsler Memory Scale-Revised score. The sliding-windows approach and graph theory analysis were used to analyze the hippocampal network based on resting state functional magnetic resonance imaging. Temporal properties and modular metrics were calculated. Two discrete and switchable states were revealed: a high modularized state (State I) and a low modularized state (State II), which corresponded to either anterior or posterior hippocampal network dominated pattern. TLE was prone to drive less State I but more State II, and the tendency was more obvious in TLE-MD. Additionally, TLE-MD showed more widespread alterations of modular properties compared with TLE-MI across two states. Furthermore, the dynamic modularity features had unique superiority in discriminating TLE-MD from TLE-MI. These findings demonstrated that state transitions and modular function of dissociable hippocampal networks were altered in TLE and more importantly, they could reflect different memory phenotypes. The trend revealed potential values of dynamic FC in elucidating the mechanism underlying memory impairments in TLE., (© 2021 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.)