Hippocampal Volume In Patients Research Articles

Remote digital cognitive assessment reveals cognitive deficits related to hippocampal atrophy in autoimmune limbic encephalitis: a cross-sectional validation study

Autoimmune limbic encephalitis (ALE) is a neurological disease characterised by inflammation of the limbic regions of the brain, mediated by pathogenic autoantibodies. Because cognitive deficits persist following acute treatment of ALE, the accurate assessment of long-term cognitive outcomes is important for clinical assessments and trials. However, evaluating cognition is costly and an unmet need exists for validated digital methods. In this cross-sectional validation study, we investigated whether a remote digital platform could identify previously characterised cognitive impairments in patients with chronic ALE and whether digital metrics would correlate with standard neuropsychological assessment and hippocampal volume. Patients with ALE who had a chronic and stable presentation and received a clinical diagnosis of ALE were recruited for this study. The cognitive performance of 21 patients with ALE and 54 age-matched healthy controls - enrolled via the University of Oxford (UK) Cognitive Neurology Lab testing programme - was assessed with a battery of 12 cognitive tasks from the Cognitron online platform. The platform was optimised with National Institute for Health and Care Research (NIHR) support to be deliverable remotely to elderly and patient groups. The primary outcome measure was behavioural performance and corresponding neuroimaging and neuropsychological assessment metrics. Between February 15, 2021, and April 21, 2022, 21 patients with ALE (mean age 63.01 years, 14 males) and 54 healthy controls (mean age 65.56 years, 23 males) completed the digital cognitive assessment. Patients with ALE performed significantly worse in memory, visuospatial abilities, executive function, and language. No impairments in digit & spatial span, target detection (attention) and emotion discrimination were observed. The global score on the online cognitive tasks correlated significantly with the established Addenbrooke's Cognitive Examination III (ACE) pen-and-paper test. Deficits in visuospatial processing and language were identified in ALE compared to controls using remote digital testing but not using the ACE, highlighting higher sensitivity of computerised testing to residual cognitive impairment. Finally, the hippocampal volumes of patients with ALE and healthy controls correlated with online cognitive scores. These findings demonstrate that subtle cognitive deficits in patients with chronic ALE, who often show full recovery in measures of disability and dependence on daily activities, are detectable using a remote online platform, which also relates to hippocampal atrophy. Such methods may facilitate the characterisation of cognitive profiles in complex neurological diseases. Future longitudinal studies designed to assess the utility of such digital methods for further clinical characterisation are needed. The Wellcome Trust, Medical Research Council, National Institute for Health Research, Rhodes Scholarship, and the Berrow Foundation Scholarship.

Collateral Damage: Neurological Correlates of Non-Fatal Overdose in the Era of Fentanyl-Xylazine

Non-fatal opioid overdoses are associated with significant morbidity. Hypoxic brain injury caused by opioid-induced respiratory depression is a key mechanism of such morbidity. For example, reports describe an amnestic syndrome in opioid users associated with acute injury to the hippocampus, a brain region that is highly susceptible to hypoxic injury. In our recent study we investigated the effects of non-fatal opioid overdose on the hippocampal volume in a well-characterized sample of opioid use disorder (OUD) patients with a history of overdose (OD) compared to those with no prior overdose (NOD). Using structural magnetic resonance imaging (MRI) and voxel-based morphometry, we observed lower hippocampal volume in patients with a history OD than in the NOD group. These findings support an association between non-fatal opioid overdose and hippocampal injury, which we hypothesize contributes to recently reported cases of OUD related amnestic syndrome. Here we review our study findings and the potential pathophysiological mechanisms underlying the acute and delayed hippocampal injury in nonfatal opioid overdose. We also discuss the implications for the risk of overdose and brain injury with the increased prevalence of fentanyl and xylazine contamination of the illicit opioid supply. Lastly, we highlight considerations for clinical management of the underappreciated neurological injury and cognitive dysfunction in OUD patients.

Neural correlates of social exclusion and overinclusion in patients with borderline personality disorder: an fMRI study

BackgroundInterpersonal difficulties of patients with borderline personality disorder (BPD) are closely related to rejection sensitivity. The aim of the present study was to gain further insight into the experience and cerebral processing of social interactions in patients with BPD by using fMRI during experimentally induced experiences of social exclusion, inclusion, and overinclusion.MethodsThe study involved 30 participants diagnosed with BPD (29 female and 1 male; age: M = 24.22, SD = 5.22) and 30 healthy controls (29 female and 1 male; age: M = 24.66, SD = 5.28) with no current or lifetime psychiatric diagnoses. In the fMRI session, all participants were asked to complete a Cyberball task that consisted of an alternating sequence of inclusion, exclusion, and overinclusion conditions.ResultsCompared to healthy controls, participants with BPD reported higher levels of inner tension and more unpleasant emotions across all experimental conditions. At the neural level, the participants with BPD showed lower recruitment of the left hippocampus in response to social exclusion (relative to the inclusion condition) than the healthy controls did. Lower recruitment of the left hippocampus in this contrast was associated with childhood maltreatment in patients with BPD. However, this difference was no longer significant when we added the covariate of hippocampal volume to the analysis. During social overinclusion (relative to the inclusion condition), we observed no significant differences in a group comparison of neural activation.ConclusionsThe results of our study suggest that patients with BPD experience more discomfort than do healthy controls during social interactions. Compared to healthy participants, patients with BPD reported more inner tension and unpleasant emotions, irrespective of the extent to which others included them in social interactions. At a neural level, the participants with BPD showed a lower recruitment of the left hippocampus in response to social exclusion than the healthy controls did. The reduced activation of this neural structure could be related to a history of childhood maltreatment and smaller hippocampal volume in patients with BPD.

Effect of Late-Stage Meniere's Disease and Vestibular Functional Impairment on Hippocampal Atrophy.

We investigated correlations among clinical features, degree of inner ear endolymphatic hydrops (EH), and hippocampal volume (HV) in different stages of Meniere's disease (MD). From February 2021 to April 2022, clinical data were collected from 99 patients (39 males, 60 females, mean age: 50.4 ± 10.0 [range: 26-69] years) with unilateral MD admitted to the Department of Vertigo Disease of Shandong ENT Hospital. The left and right ears were affected in 64 and 35 patients, respectively. There were 50 and 49 cases in early (Stages 1, 2) and late stages (Stages 3, 4), respectively. Fifty healthy participants were included as controls. Audiovestibular function test results, EH grading using gadolinium-enhanced magnetic resonance imaging (MRI), and HV determined on MRI were analyzed for patients at different stages of MD. Between-group comparisons of early and late MD revealed significant differences in the disease course, vestibular function (VF), degree of EH, and HV. There were no significant between-group differences based on age, sex, affected side, subjective degree of dizziness, hospital anxiety, or depression. Mean HV in patients with early-stage MD was correlated with the canal paresis value of the caloric test and pure tone hearing threshold, HV in late-stage patients was correlated with vestibular EH. Patients with late-stage MD exhibited severe auditory and VF impairments, increased EH, and atrophy of the HV. More advanced disease was associated with greater vestibular damage and degree of EH. 3 Laryngoscope, 134:410-418, 2024.

Mediation of Reduced Hippocampal Volume by Cerebral Amyloid Angiopathy in Pathologically Confirmed Patients with Alzheimer's Disease.

Hippocampal atrophy in cerebral amyloid angiopathy (CAA) has been reported to be similar to that in Alzheimer's disease (AD). To evaluate if CAA pathology partly mediates reduced hippocampal volume in patients with AD. Patients with a clinical diagnosis of AD and neuropathological confirmation of AD+/-CAA in the National Alzheimer's Coordinating Center database were included in the study. The volumes of temporal lobe structures were calculated on T1-weighted imaging (T1-MRI) using automated FreeSurfer software, from images acquired on average 5 years prior to death. Multivariate regression analysis was performed to compare brain volumes in four CAA groups. The hippocampal volume on T1-MRI was correlated with Clinical Dementia Rating sum of boxes (CDRsb) score, apolipoprotein E (APOE) genotype, and hippocampal atrophy at autopsy. The study included 231 patients with no (n = 45), mild (n = 70), moderate (n = 67), and severe (n = 49) CAA. Among the four CAA groups, patients with severe CAA had a smaller mean left hippocampal volume (p = 0.023) but this was not significant when adjusted for APOE ɛ4 (p = 0.07). The left hippocampal volume on MRI correlated significantly with the hippocampal atrophy grading on neuropathology (p = 0.0003). Among patients with severe CAA, the left hippocampal volume on T1-MRI: (a) decreased with an increase in the number of APOE ɛ4 alleles (p = 0.04); but (b) had no evidence of correlation with CDRsb score (p = 0.57). Severe CAA was associated with smaller left hippocampal volume on T1-MRI up to five years prior to death among patients with neuropathologically confirmed AD. This relationship was dependent on APOE ɛ4 genotype.

Subfield-specific longitudinal changes of hippocampal volumes in patients with early-stage bipolar disorder.

The hippocampus is a heterogeneous structure composed of biologically and functionally distinct subfields. Hippocampal aberrations are proposed to play a fundamental role in the etiology of psychotic symptoms. Bipolar disorder (BPD) has substantial overlap in symptomatology and genetic liability with schizophrenia (SZ), and reduced hippocampal volumes, particularly at the chronic illness stages, are documented in both disorders. Studies of hippocampal subfields in the early stage of BPD are limited and cross-sectional findings to date report no reduction in hippocampal volumes. To our knowledge, there have been no longitudinal studies of BPD evaluating hippocampal volumes in the early phase of illness. We investigated the longitudinal changes in hippocampal regions and subfields in BPD mainly and in early stage of psychosis (ESP) patients more broadly and compared them to those in controls (HC). Baseline clinical and structural MRI data were acquired from 88 BPD, from a total of 143 ESP patients, and 74 HCs. Of those, 66 participants (23 HC, 43 patients) completed a 12-month follow-up visit. The hippocampus regions and subfields were segmented using Freesurfer automated pipeline. We found general baseline deficits in hippocampal volumes among BPD and ESP cohorts. Both cohorts displayed significant increases in the anterior hippocampal region and dentate gyrus compared with controls. Additionally, antipsychotic medications were positively correlated with the posterior region at baseline. These findings highlight brain plasticity in BPD and in ESP patients providing evidence that deviations in hippocampal volumes are adaptive responses to atypical signaling rather than progressive degeneration.

Magnetic resonance volumetric analysis of hippocampal lobe in children aged 6 years or younger presenting with seizures

Background: Magnetic Resonance (MR) imaging studies are sufficient for detection of gross Hippocampal Atrophy (HA), subtle HA that may characterize early disease is often missed. Quantitative MR imaging/ MR volumetry can depict the presence and laterality of HA in epilepsy with accuracy rates that may exceed those achieved with visual inspection of clinical MR imaging studies. Materials and Methods: The study comprised of Children at or below 6 years of age admitted in pediatric ward for seizure from July 2019 to December 2020 in Mahatma Gandhi Medical College Hospital and Research Institute presenting with seizures, admitted to pediatric department, and referred to radiodiagnosis for MRI. Complete case history including the socio-demographic data and other medical conditions of the patient was recorded. Results: The maximum no of patients were recorded in the age range of 13-24 years, with a slight male predominance. 44.76% patients suffering from generalized seizures, followed by 35.24% with focal seizures & 20% with undetermined form of seizures. Mean right & left hippocampal volume was found to be 2.572 & 2.4168 respectively. The mean right hippocampal volume in patients suffering from focal, generalized & undetermined patients was found to be 2.56, 2.53 & 2.67, & on left side it was 2.34, 2.42 & 2.45 respectively. The mean right hippocampal volume in patients as per the frequency/episode of 1-3, 4-6, 1-9 & 10 & above per month was found to be 2.6, 2.48, 2.41 & 2.685 & on left side it was 2.44, 2.33, 2.35 & 2.65. Conclusion: The use of MRI has been well-established as a reliable marker for the assessment of the mean volume of the hippocampus which is commonly seen to be involved in patients with seizures. We found a correlation between the mean hippocampal volume against the frequency of seizures wherein there was an increase in the volume with an increase in the frequency of seizures. We recommend more studies to understand these associations as there are deficit in terms of these parameters.

NIMG-76. MORPHOLOGIC CHANGES TO THE HIPPOCAMPI FOLLOWING SURGICAL RESECTION AND ADJUVANT CHEMORADIATION IN PATIENTS WITH HIGH GRADE TEMPORAL GLIOMAS

Abstract BACKGROUND The hippocampus is known to remodel in pathologic conditions including epilepsy and Alzheimer’s disease. Literature investigating the effect of high-grade gliomas (HGGs) on the hippocampus following resection and adjuvant chemoradiation are limited; no study has evaluated these effects in tumors exclusively in the temporal lobe. METHODS A retrospective chart review was conducted on 30 patients with temporal HGGs who underwent craniotomy for resection with adjuvant RT and TMZ. Brainlab Elements was used to manually contour bilateral hippocampal gray matter volumes in the subgranular zone using T1-precontrast MRI sequences (1.5 mm thickness or less) pre-resection and at time of most recent follow up. These volumes were compared using a student’s t-test with significance set at p< 0.05. RESULTS Average follow up time was 23.5 months from initial resection. Average pre-treatment hippocampal volumes in this temporal glioma cohort compared to healthy controls from prior studies were 2.93 vs 2.83 cm3 (right, p=0.31) and 2.78 vs 2.76 cm3 (left, p=0.39) respectively. Pre vs post resection right hippocampal volumes in patients with right sided lesions were 2.59 vs 1.75 cm3 (p=.002). Left hippocampal volumes in patients with left sided tumors were 2.99 vs 1.64 cm3 pre and post resection respectively(p=0.0009). No significant differences in hippocampal volumes contralateral to the tumor side were found following treatment (p=0.31 and 0.07 for right and left hippocampi respectively). CONCLUSIONS Temporal gliomas are in close anatomic proximity to the hippocampi also may invade and/or disrupt local circuits which output to the hippocampi. Resection and chemoradiation are correlated with decreased hippocampal volumes ipsilateral to the primary locus of disease. Further characterization of hippocampal subregions, particularly the dentate gyrus, in addition to results of neuropsychiatric testing pre and post treatment are necessary to better elucidate the clinical implications of these morphologic changes and the putative functional networks which underlie them.

Assessment of brain and hippocampal volume in patients with Cushing's disease.

The purpose of this study was to assess the volumes of the hippocampus, grey matter, and the whole brain in patients with active Cushing's disease compared to a control group. We included 36 patients diagnosed with Cushing's disease, with pituitary magnetic resonance imaging (MRI) performed as a standard preoperative assessment. The sample size of the control group was 26 persons. MRI studies were acquired with a 3.0 Tesla MR scanner equipped with a 24-channel head coil. The MRI study protocol included a pre-contrast 3D T1-weighted gradient sequence. Volumetric segmentation of the brain structures was performed using version 6.0 of the FreeSurfer software. We observed statistically significant reduction in the grey matter volume in the study group as compared to the control group (p < 0.001), with no significant differences in the volume of the whole brain (p = 0.104), left hippocampus (p = 0.790), and right hippocampus (p = 0.517). There was a strong positive correlation between grey matter volume and brain volume (r = 0.75, p < 0.001), independent of the study group. The study showed unevenly distributed brain atrophy in patients suffering from Cushing's disease, with no significant hippocampal atrophy. Significant atrophy was observed within the grey matter, potentially constituting a preliminary stage of whole-brain atrophy.

Chronic clomipramine treatment increases hippocampal volume in rats exposed to chronic unpredictable mild stress

It is well known that neuroinflammation is closely related to the pathophysiology of depression. Due to individual differences in clinical research, the reduction of hippocampal volume in patients with depression is still controversial. In this experiment, we studied a typical kind of tricyclic antidepressant, clomipramine. We designed a series of experiments to find its role in depressive-like behavior, hippocampal neuroinflammation as well as hippocampal volume changes induced by chronic unpredictable mild stress (CMS). Rats exhibited defective behavior and hippocampal neuroinflammation after 12 weeks of CMS, which included elevated expression of cleaved interleukin-1β (IL-1β) and NLRP3 inflammasome together with the activation of microglia. Rats exposed to CMS showed weakened behavioral defects, reduced expression of IL-18, IL-6, and IL-1β along with reversed activation of microglia after clomipramine treatment. This indicates that the antidepressant effect of clomipramine may be related to the reduced expression of NLRP3 inflammasome and cleaved IL-1β. Moreover, we found an increased hippocampal volume in rats exposed to CMS after clomipramine treatment while CMS failed to affect hippocampal volume. All these results indicate that the NLRP3 inflammasome of microglia in the hippocampus is related to the antidepressant effects of clomipramine and CMS-induced depressive-like behavior in rats.

Does Hippocampal Volume in Patients with Posttraumatic Stress Disorder Vary by Trauma Type?

Posttraumatic stress disorder (PTSD) is a debilitating disorder that can develop after experiencing a traumatic event and is, in part, characterized by memory disturbances. Given its important role in learning and memory, the hippocampus has been studied extensively in PTSD using volumetric neuroimaging techniques. However, the results of these studies are mixed. The variability in findings across studies could arise from differences in samples with regard to trauma type, but this connection has not yet been formally assessed. To assess this question, we conducted (1) mixed-effects meta-analyses to replicate previous meta-analytic findings of significant differences in hippocampal volumes in PTSD groups versus two different types of control groups (trauma-exposed and -unexposed groups), and (2) mixed-effects subgroup and meta-regression analyses to determine whether trauma type moderated these hippocampal volume differences. Overall, the PTSD groups showed significantly smaller right hippocampal volumes than both control groups and significantly smaller left hippocampal volumes than trauma-unexposed control groups. Subgroup and meta-regression analyses revealed that trauma type did not moderate the effect seen between PTSD and trauma-exposed non-PTSD groups but did moderate the effect between the PTSD and trauma-unexposed control groups: studies that contained participants with PTSD related to combat trauma exhibited significantly smaller effect sizes for right hippocampal volumes compared to the interpersonal violence and "other" trauma-type groups with PTSD. These findings suggest that trauma type may moderate hippocampal volume in trauma-exposed individuals but not in those with PTSD.

Hippocampal volume in patients with bilateral and unilateral peripheral vestibular dysfunction

Previous studies have found that peripheral vestibular dysfunction is associated with altered volumes in different brain structures, especially in the hippocampus. However, published evidence is conflicting. Based on previous findings, we compared hippocampal volume, as well as supramarginal, superior temporal, and postcentral gyrus in a sample of 55 patients with different conditions of peripheral vestibular dysfunction (bilateral, chronic unilateral, acute unilateral) to 39 age- and sex-matched healthy controls. In addition, we explored deviations in gray-matter volumes in hippocampal subfields. We also analysed correlations between morphometric data and visuo-spatial performance. Patients with vestibular dysfunction did not differ in total hippocampal volume from healthy controls. However, a reduced volume in the right presubiculum of the hippocampus and the left supramarginal gyrus was observed in patients with chronic and acute unilateral vestibular dysfunction, but not in patients with bilateral vestibular dysfunction. No association of altered volumes with visuo-spatial performance was found. An asymmetric vestibular input due to unilateral vestibular dysfunction might lead to reduced central brain volumes that are involved in vestibular processing.

Impact of Frailty on Hippocampal Volume in Patients with Chronic Obstructive Pulmonary Disease.

Brain frailty may be related to the pathophysiology of poor clinical outcomes in chronic obstructive pulmonary disease (COPD). This study examines the relationship between hippocampal subfield volumes and frailty and depressive symptoms, and their combined association with quality of life (QOL) in patients with COPD. The study involved 40 patients with COPD. Frailty, depressive symptoms and QOL were assessed using Kihon Checklist (KCL), Hospital Anxiety and Depression Scale (HADS), and World Health Organization Quality of Life Assessment (WHO/QOL-26). Anatomical MRI data were acquired, and volumes of the hippocampal subfields were obtained using FreeSurfer (version 6.0). Statistically, HADS score had significant association with WHO/QOL-26 and KCL scores. KCL scores were significantly associated with volumes of left and right whole hippocampi, presubiculum and subiculum, but HADS score had no significant association with whole hippocampi or hippocampal subfield volumes. Meanwhile, WHO/QOL-26 score was significantly associated with volume of the left CA1. There was a significant association between frailty, depression, and QOL. Hippocampal pathology was related to frailty and, to some extent, with QOL in patients with COPD. Our results suggest the impact of frailty on hippocampal volume and their combined associations with poor QOL in COPD.

Hippocampal magnetic resonance imaging in focal onset seizure with impaired awareness\u2014descriptive study from tertiary care centre in southern part of India

BackgroundTemporal lobe epilepsy is the most common type of focal onset seizure. Focal onset seizure with impaired awareness, previously known as complex partial seizure (CPS), account for 18–40% of all seizure types. Hippocampal sclerosis (HS) is the most common cause of temporal lobe epilepsy, which produces focal onset seizure with impaired awareness. It may be detected in MRI visually, but bilateral abnormalities are better identified using volumetric analysis.We aimed to compare hippocampal volume in patients with focal onset seizure with impaired awareness visually and quantitatively.MethodologyThis cross-sectional study includes clinically diagnosed cases of 56 focal onset seizure with impaired awareness undergoing MRI at a tertiary teaching hospital in the southern part of India for a duration of 18 months from February 2018 to August 2019.ResultsOut of 53 patients studied using 1.5 T MRI brain with seizure protocols, hippocampal atrophy was identified visually in 13 (24.5%) on the right side, 9 (16.98%) on the left side, and in 6 (11.32%) bilaterally. However, with volumetry, hippocampal atrophy (not taking T2 signal change) was detected in 15 (28.30%) on the right side, 10 (18.86%) on the left side, and in 7 (13.20%) bilaterally. Hippocampal volumes between ipsilateral and contralateral seizure focus were found to have no significant difference (p-0.84).ConclusionsThough visual analysis is efficient in the diagnosis of pathology, MR volumetry may be used as an expert eye in cases of subtle volume loss.

The association of matrix metalloproteinase 9 (MMP9) with hippocampal volume in schizophrenia: a preliminary MRI study.

Matrix metalloproteinases 9 (MMP9) are enzymes involved in regulating neuroplasticity in the hippocampus. This, combined with evidence for disrupted hippocampal structure and function in schizophrenia, has prompted our current investigation into the relationship between MMP9 and hippocampal volumes in schizophrenia. 34 healthy individuals (mean age = 32.50, male = 21, female = 13) and 30 subjects with schizophrenia (mean age = 33.07, male = 19, female = 11) underwent a blood draw and T1-weighted magnetic resonance imaging. The hippocampus was automatically segmented utilizing FreeSurfer. MMP9 plasma levels were measured with ELISA. ANCOVAs were conducted to compare MMP9 plasma levels (corrected for age and sex) and hippocampal volumes between groups (corrected for age, sex, total intracranial volume). Spearman correlations were utilized to investigate the relationship between symptoms, medication, duration of illness, number of episodes, and MMP9 plasma levels in patients. Last, we explored the correlation between MMP9 levels and hippocampal volumes in patients and healthy individuals separately. Patients displayed higher MMP9 plasma levels than healthy individuals (F(1, 60) = 21.19, p < 0.0001). MMP9 levels correlated with negative symptoms in patients (R = 0.39, p = 0.035), but not with medication, duration of illness, or the number of episodes. Further, patients had smaller left (F(1,59) = 9.12, p = 0.0040) and right (F(1,59) = 6.49, p = 0.013) hippocampal volumes. Finally, left (R = -0.39, p = 0.034) and right (R = -0.37, p = 0.046) hippocampal volumes correlated negatively with MMP9 plasma levels in patients. We observe higher MMP9 plasma levels in SCZ, associated with lower hippocampal volumes, suggesting involvement of MMP9 in the pathology of SCZ. Future studies are needed to investigate how MMP9 influences the pathology of SCZ over the lifespan, whether the observed associations are specific for schizophrenia, and if a therapeutic modulation of MMP9 promotes neuroprotective effects in SCZ.

Lower Hippocampal Volume in Patients with Schizophrenia and Bipolar Disorder: A Quantitative MRI Study.

Since patients with schizophrenia (SZ) and bipolar disorder (BD) share many biological features, detecting biomarkers that differentiate SZ and BD patients is crucial for optimized treatments. High-resolution magnetic resonance imaging (MRI) is suitable for detecting subtle brain structural differences in patients with psychiatric disorders. In the present study, we adopted a neuroanatomically defined and manually delineated region of interest (ROI) method to evaluate the amygdalae, hippocampi, Heschl’s gyrus (HG), and planum temporale (PT), because these regions are crucial in the development of SZ and BD. ROI volumes were measured using high resolution MRI in 31 healthy subjects (HS), 23 SZ patients, and 21 BD patients. Right hippocampal volumes differed significantly among groups (HS > BD > SZ), whereas left hippocampal volumes were lower in SZ patients than in HS and BD patients (HS = BD > SZ). Volumes of the amygdalae, HG, and PT did not differ among the three groups. For clinical correlations, there were no significant associations between ROI volumes and demographics/clinical symptoms. Our study revealed significant lower hippocampal volume in patients with SZ and BD, and we suggest that the right hippocampal volume is a potential biomarker for differentiation between SZ and BD.

Hippocampal subfield and anterior-posterior segment volumes in patients with sporadic amyotrophic lateral sclerosis

Neuroimaging studies of hippocampal volumes in patients with amyotrophic lateral sclerosis (ALS) have reported inconsistent results. Our aims were to demonstrate that such discrepancies are largely due to atrophy of different regions of the hippocampus that emerge in different disease stages of ALS and to explore the existence of co-pathology in ALS patients. We used the well-validated King’s clinical staging system for ALS to classify patients into different disease stages. We investigated in vivo hippocampal atrophy patterns across subfields and anterior-posterior segments in different King’s stages using structural MRI in 76 ALS patients and 94 health controls (HCs). The thalamus, corticostriatal tract and perforant path were used as structural controls to compare the sequence of alterations between these structures and the hippocampal subfields. Compared with HCs, ALS patients at King’s stage 1 had lower volumes in the bilateral posterior subiculum and presubiculum; ALS patients at King’s stage 2 exhibited lower volumes in the bilateral posterior subiculum, left anterior presubiculum and left global hippocampus; ALS patients at King’s stage 3 showed significantly lower volumes in the bilateral posterior subiculum, dentate gyrus and global hippocampus. Thalamic atrophy emerged at King’s stage 3. White matter tracts remained normal in a subset of ALS patients. Our study demonstrated that the pattern of hippocampal atrophy in ALS patients varies greatly across King’s stages. Future studies in ALS patients that focus on the hippocampus may help to further clarify possible co-pathologies in ALS.

Automated hippocampal segmentation improved by convolutional neural network approach in participants with a history of cerebrovascular accident

AbstractBackgroundCerebrovascular accidents (CVA) are risk factors for dementia, including Alzheimer’s disease (AD; Arvanitakis et al., 2016). Hippocampal atrophy is observed in both CVA (Gemmel et al., 2012) and AD (Braak &amp; Braak, 1991) patients. Thus, the hippocampus may be an important biomarker for CVA patients with high AD‐risk. FreeSurfer, a commonly used automated hippocampal segmentation method to study post‐CVA hippocampal volume (Khlif et al., 2019), uses an atlas‐based approach, making it more likely to fail in the presence of CVA lesions (Yang et al., 2016). Two recent convolutional neural network‐based (CNN) hippocampal segmentation algorithms, Hippodeep (Thyreau et al., 2018) and Hippmapp3r (Goubran et al., 2019), are more flexible for post‐CVA anatomical changes since they do not rely on a single atlas. However, they have not been widely tested in CVA populations. Here, we compare the segmentation accuracy of FreeSurfer, Hippodeep, and Hippmapp3r in participants with a history of CVA.Method30 T1‐weighted structural brain MRIs from CVA participants with varying lesion sizes (0.43‐181.5 cc) in the Anatomical Tracings of Lesions After Stroke dataset (Liew et al., 2018) were used to compare FreeSurfer, Hippodeep, and Hippmapp3r to manual segmentations. Accuracy was measured as spatial overlap between each automated and manual segmentation using the Dice Coefficient (DC). An ANOVA was used to test for DC differences across methods.ResultDC significantly differed by segmentation method (F‐value=178.3;p‐value&lt;2.10x‐16). Ipsilesional results: Hippodeep DC was significantly greater than FreeSurfer DC (p‐value=1.03x10‐17;t‐value=18.7) but not significantly different from Hippmapp3r DC. Contralesional results: Hippmapp3r DC was significantly greater than both Hippodeep (p‐value=9.53x10‐4;t‐value=4.52) and FreeSurfer (p‐value=4.68x10‐21;t‐value=24.8;Figure 1).ConclusionHippodeep and Hippmapp3r segmentations had significantly better accuracy than FreeSurfer, although all methods had a DC &gt;0.7 (recommended threshold for good segmentation overlap; Zou et al., 2004). For ipsilesional segmentation accuracy, the two CNN methods did not significantly differ, while for contralesional segmentations, Hippmapp3r performed best. Future studies may benefit from using CNN approaches to more accurately estimate hippocampal volumes in patients with CVA with high AD risk.

The environment contributes more than genetics to smaller hippocampal volume in Posttraumatic Stress Disorder (PTSD)

BackgroundStudies using structural magnetic resonance imaging (MRI) volumetrics showed smaller hippocampal volume in patients with post-traumatic stress disorder (PTSD). These studies were cross-sectional and did not address whether smaller volume is secondary to stress-induced damage, or whether pre-existing factors account for the findings. The purpose of this study was to use a co-twin case control design to assess the relative contribution of genetic and environmental factors to hippocampal volume in PTSD. MethodsMonozygotic (N = 13 pairs) and dizygotic (N = 21 pairs) twins with a history of Vietnam Era military service, where one brother went to Vietnam and developed PTSD, while his brother did not go to Vietnam or develop PTSD, underwent MR imaging of the brain. Structural MRI scans were used to manually outline the left and right hippocampus on multiple coronal slices, add the areas and adjust for slice thickness to determine hippocampal volume. ResultsTwins with Vietnam combat-related PTSD had a mean 11% smaller right hippocampal volume in comparison to their twin brothers without combat exposure or PTSD (p < .05). There was no significant interaction by zygosity, suggesting that this was not a predisposing risk factor or genetic effect. ConclusionsThese findings are consistent with smaller hippocampal volume in PTSD, and suggest that the effects are primarily due to environmental effects such as the stress of combat.

HHV-6 and hippocampal volume in patients with mesial temporal sclerosis.

ObjectiveTo study the effects of human herpes virus 6 (HHV‐6) on the hippocampal volume in patients with mesial temporal sclerosis (MTS).BackgroundHHV‐6 may play an etiologic role in MTS. Previous studies found a possible association with febrile status epilepticus. Several investigators have reported a higher prevalence of HHV‐6 in MTS resections compared to other epilepsy etiologies.Design/MethodsWe used FreeSurfer to segment cortical structures and obtain whole hippocampal and subfield volumes in 41 patients with intractable epilepsy. In addition, an investigator blinded to other data traced hippocampi manually on each slice. The main study outcome measure was the asymmetry index (AI) between hippocampal volumes ipsilateral and contralateral to seizure foci compared between HHV‐6 positive and negative patients. Viral DNA was isolated from fresh brain tissue obtained at temporal lobectomy. For 25 patients, viral detection was performed using quantitative real‐time PCR specific for HHV‐6A and HHV‐6B. For 16 patients, viral DNA detection was performed using digital droplet PCR specific for HHV‐6A and HHV‐6B.ResultsTwenty‐two patients were positive (14 of 25 tested with real‐time PCR, and 8 of 16 with digital droplet PCR), and 19 negatives for HHV‐6. HHV‐6 negative patients had significantly greater AI and lower total hippocampal volume ipsilateral to seizure foci than HHV‐6 positive patients. Epilepsy duration and age of onset did not affect results.InterpretationOur data suggest multiple potential etiologies for MTS. HHV‐6 may have a less severe effect on the hippocampus than other etiologies.