Differences In Hippocampal Volume Research Articles

Effects of repeated exposure to different concentrations of sevoflurane on the neonatal mouse hippocampus

Background and objectivesDeveloping brain is more vulnerable to environmental risk than is the developed brain. We evaluated the effects of repeated exposure to different concentrations of sevoflurane on the neonatal mouse hippocampus using stereological methods. MethodsEighteen neonatal male mice were randomly divided into three groups. Group A, inhaled sevoflurane at a concentration of 1.5%; Group B, inhaled sevoflurane at a concentration of 3%; and Group C (control group), inhaled only 100% oxygen. Treatments were applied for 30min a day for 7 consecutive days. The hippocampal volume, dendrite length, number of neurons, and number of glial cells were evaluated in each group using stereological estimations. ResultsWe identified a ∼2% reduction in the volume of the hippocampus in Group A compared to Group C. Mean hippocampal volume was ∼11% smaller in Group B than it was in Group C. However, these differences in hippocampal volume between the groups were not statistically significant (p>0.05 for all). As for the number of neurons, we found significantly fewer neurons in Group A (∼29% less) and Group B (∼43% less) than we did in Group C (p<0.05 for both). The dendrite length was ∼8% shorter in Group A and ∼11% shorter in Group B than it was in Group C. ConclusionsRepeated exposure to sevoflurane, regardless of the concentration, reduced the volume of the neonatal mouse hippocampus, as well as the number of neurons and dendrite length.

It's All in the Details: Relations Between Young Children's Developing Pattern Separation Abilities and Hippocampal Subfield Volumes.

The ability to keep similar experiences separate in memory is critical for forming unique and lasting memories, as many events share overlapping features (e.g., birthday parties, holidays). Research on memory in young children suggests their memories often lack high-resolution details, i.e., show impoverished pattern separation (PS). Recently developed assessments of PS suitable for children allow us to relate the formation of distinct, detailed memories for the development of the hippocampus, a neural structure critical for this ability in adults. The hippocampus displays a protracted developmental profile and underlies the ability to form detailed memories. This study examined age-related differences in hippocampal subfield volumes in 4- to 8-year-old children and relations with performance on a mnemonic similarity task (MST) designed to index memory specificity. Results revealed age-moderated associations between MST performance and cornu ammonis 2-4/dentate gyrus subfields. Specifically, age-related differences in the ability to form detailed memories tracked with normative patterns of volume increases followed by reductions over this age range. That is, greater volume correlated with better performance in younger children, whereas smaller volume correlated with better performance in older children. These findings support the hypothesis that developmental differences in hippocampal circuitry contribute to age-related improvements in detailed memory formation during this period.

Lower Prefrontal and Hippocampal Volume and Diffusion Tensor Imaging Differences Reflect Structural and Functional Abnormalities in Abstinent Individuals with Alcohol Use Disorder.

Alcohol use disorder (AUD) is known to have adverse effects on brain structure and function. Multimodal assessments investigating volumetric, diffusion, and cognitive characteristics may facilitate understanding of the consequences of long-term alcohol use on brain circuitry, their structural impairment patterns, and their impact on cognitive function in AUD. Voxel- and surface-based volumetric estimations, diffusion tensor imaging (DTI), and neuropsychological tests were performed on 60 individuals: 30 abstinent individuals with AUD (DSM-IV) and 30 healthy controls. Group differences in the volumes of cortical and subcortical regions, fractional anisotropy (FA), axial and radial diffusivities (AD and RD, respectively), and performance on neuropsychological tests were analyzed, and the relationship among significantly different measures was assessed using canonical correlation. AUD participants had significantly smaller volumes in left pars orbitalis, right medial orbitofrontal, right caudal middle frontal, and bilateral hippocampal regions, lower FA in 9 white matter (WM) regions, and higher FA in left thalamus, compared to controls. In AUD, lower FA in 6 of 9 WM regions was due to higher RD and due to lower AD in the left external capsule. AUD participants scored lower on problem-solving ability, visuospatial memory span, and working memory. Positive correlations of prefrontal cortical, left hippocampal volumes, and FA in 4 WM regions with visuospatial memory performance and negative correlation with lower problem-solving ability were observed. Significant positive correlation between age and FA was observed in bilateral putamen. Findings showed specific structural brain abnormalities to be associated with visuospatial memory and problem-solving ability-related impairments observed in AUD. Higher RD in 6 WM regions suggests demyelination, and lower AD in left external capsule suggests axonal loss in AUD. The positive correlation between FA and age in bilateral putamen may reflect accumulation of iron depositions with increasing age.

Alteration to hippocampal volume and shape confined to cannabis dependence: a multi‐site study

Cannabis use is highly prevalent and often considered to be relatively harmless. Nonetheless, a subset of regular cannabis users may develop dependence, experiencing poorer quality of life and greater mental health problems relative to non-dependent users. The neuroanatomy characterizing cannabis use versus dependence is poorly understood. We aimed to delineate the contributing role of cannabis use and dependence on morphology of the hippocampus, one of the most consistently altered brain regions in cannabis users, in a large multi-site dataset aggregated across four research sites. We compared hippocampal volume and vertex-level hippocampal shape differences (1) between 121 non-using controls and 140 cannabis users; (2) between 106 controls, 50 non-dependent users and 70 dependent users; and (3) between a subset of 41 controls, 41 non-dependent users and 41 dependent users, matched on sample characteristics and cannabis use pattern (onset age and dosage). Cannabis users did not differ from controls in hippocampal volume or shape. However, cannabis-dependent users had significantly smaller right and left hippocampi relative to controls and non-dependent users, irrespective of cannabis dosage. Shape analysis indicated localized deflations in the superior-medial body of the hippocampus. Our findings support neuroscientific theories postulating dependence-specific neuroadaptations in cannabis users. Future efforts should uncover the neurobiological risk and liabilities separating dependent and non-dependent use of cannabis.

The long-term effect of perinatal asphyxia on hippocampal volumes.

Hypoxic-ischemic encephalopathy (HIE) in term-born infants can lead to memory problems. The hippocampus is important for long-term episodic memory. The primary aim was to investigate the effect of HIE on hippocampal volumes in 9- to 10-year-old children. The secondary aim was to investigate the association between hippocampal volumes and previously found impaired memory and cognitive functions in the current cohort. In total 26 children with mild HIE, 26 with moderate HIE, and 37 controls were included. The intelligence quotient (IQ) and memory were tested. A 3D-volumetric MRI was obtained. Brain segmentation was performed for hippocampal volumes and intracranial volume. The differences in hippocampal volumes, memory, and IQ between the groups were determined. Multivariable linear regression analyses were performed, including hippocampal volume as a percentage of intracranial volume as a dependent variable. Smaller hippocampal volumes were found in moderate HIE (p < 0.001), with a trend toward smaller volumes in mild HIE, compared to controls. In multivariable linear regression analysis, hippocampal volume as a percentage of intracranial volume was significantly associated with long-term visuospatial memory. Children with moderate HIE had smaller hippocampal volumes than controls, with a trend toward smaller volumes following mild HIE. Reduced hippocampal volumes were associated with poorer long-term visuospatial memory.

Plasma amyloid-\u03b2 levels, cerebral atrophy and risk of dementia: a population-based study

BackgroundPlasma amyloid-β (Aβ) levels are increasingly studied as a potential accessible marker of cognitive impairment and dementia. However, it remains underexplored whether plasma Aβ levels including the novel Aβ peptide 1–38 (Aβ1–38) relate to preclinical markers of neurodegeneration and risk of dementia. We investigated the association of plasma Aβ1–38, Aβ1–40, and Aβ1–42 levels with imaging markers of neurodegeneration and risk of dementia in a prospective population-based study.MethodsWe analyzed plasma Aβ levels in 458 individuals from the Rotterdam Study. Brain volumes, including gray matter, white matter, and hippocampus, were computed on the basis of 1.5-T magnetic resonance imaging (MRI). Dementia and its subtypes were defined on the basis of internationally accepted criteria.ResultsA total of 458 individuals (mean age, 67.8 ± 7.7 yr; 232 [50.7%] women) with baseline MRI scans and incident dementia were included. The mean ± SD values of Aβ1–38, Aβ1–40, and Aβ1–42 (in pg/ml) were 19.4 ± 4.3, 186.1 ± 35.9, and 56.3 ± 6.2, respectively, at baseline. Lower plasma Aβ1–42 levels were associated with smaller hippocampal volume (mean difference in hippocampal volume per SD decrease in Aβ1–42 levels, − 0.13; 95% CI, − 0.23 to − 0.04; p = 0.007). After a mean follow-up of 14.8 years (SD, 4.9; range, 4.1–23.5 yr), 79 persons developed dementia, 64 of whom were diagnosed with Alzheimer’s disease (AD). Lower levels of Aβ1–38 and Aβ1–42 were associated with increased risk of dementia, specifically AD (HR for AD per SD decrease in Aβ1–38 levels, 1.39; 95% CI, 1.00–2.16; HR for AD per SD decrease in Aβ1–42 levels, 1.35; 95% CI, 1.05–1.75) after adjustment for age, sex, education, cardiovascular risk factors, apolipoprotein E ε4 allele carrier status, and other Aβ isoforms.ConclusionsOur results show that lower plasma Aβ levels were associated with risk of dementia and incident AD. Moreover, lower plasma Aβ1–42 levels were related to smaller hippocampal volume. These results suggest that plasma Aβ1–38 and Aβ1–42 maybe useful biomarkers for identification of individuals at risk of dementia.

The EADC-ADNI harmonized protocol for hippocampal segmentation: A validation study

Recently, a group of major international experts have completed a comprehensive effort to efficiently define a harmonized protocol for manual hippocampal segmentation that is optimized for Alzheimer's research (known as the EADC-ADNI Harmonized Protocol (the HarP)). This study compares the HarP with one of the widely used hippocampal segmentation protocols (Pruessner, 2000), based on a single automatic segmentation method trained separately with libraries made from each manual segmentation protocol. The automatic segmentation conformity with the corresponding manual segmentation and the ability to capture Alzheimer's disease related hippocampal atrophy on large datasets are measured to compare the manual protocols. In addition to the possibility of harmonizing different procedures of hippocampal segmentation, our results show that using the HarP, the automatic segmentation conformity with manual segmentation is also preserved (Dice's κ=0.88,κ=0.87 for Pruessner and HarP respectively (p = 0.726 for common training library)). Furthermore, the results show that the HarP can capture the Alzheimer's disease related hippocampal volume differences in large datasets. The HarP-derived segmentation shows large effect size (Cohen's d = 1.5883) in separating Alzheimer's Disease patients versus normal controls (AD:NC) and medium effect size (Cohen's d = 0.5747) in separating stable versus progressive Mild Cognitively Impaired patients (sMCI:pMCI). Furthermore, the area under the ROC curve for a LDA classifier trained based on age, sex and HarP-derived hippocampal volume is 0.8858 for AD:NC, and for 0.6677 sMCI:pMCI. These results show that the harmonized protocol-derived labels can be widely used in clinic and research, as a sensitive and accurate way of delineating the hippocampus.

Clinical and imaging correlates of amyloid deposition in dementia with Lewy bodies.

ABSTRACT Background: Amyloid deposition is common in dementia with Lewy bodies, but its pathophysiological significance is unclear. Objective: The objective of this study was to investigate the relationship between amyloid deposition and clinical profile, gray matter volume, and brain perfusion in dementia with Lewy bodies. Methods: Dementia with Lewy bodies (n = 37), Alzheimer's disease (n = 20), and controls (n = 20) underwent a thorough clinical assessment, 3T MRI, and early‐ and late‐phase 18F‐Florbetapir PET‐CT to assess cortical perfusion and amyloid deposition, respectively. Amyloid scans were visually categorized as positive or negative. Image analysis was carried out using statistical parametric mapping (SPM) 8. Results: There were no significant differences between amyloid‐positive and amyloid‐negative dementia with Lewy bodies cases in age (P = .78), overall cognitive impairment (P = .83), level of functional impairment (P = .80), or any other clinical or cognitive scale. There were also no significant differences in hippocampal or gray matter volumes. However, amyloid‐positive dementia with Lewy bodies cases had lower medial temporal lobe perfusion (P = .03) than amyloid‐negative cases, although a combination of medial temporal lobe perfusion, hippocampal volume, and cognitive measures was unable to accurately predict amyloid status in dementia with Lewy bodies. Conclusions: Amyloid deposition was not associated with differences in clinical or neuropsychological profiles in dementia with Lewy bodies, but was associated with imaging evidence of medial temporal lobe dysfunction. The presence of amyloid in dementia with Lewy bodies cannot be identified on the basis of clinical and other imaging features and will require direct assessment via PET imaging or CSF. © 2018 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.

O6.1. HIPPOCAMPAL VOLUME IN ADOLESCENTS WITH PERSISTENT PSYCHOTIC EXPERIENCES: A LONGITUDINAL POPULATION-BASED MRI STUDY

BackgroundIndividuals with schizophrenia show significant brain morphological abnormalities. The ENIGMA consortium identified that patients with schizophrenia had smaller hippocampus, amygdala, thalamus, accumbens and intracranial volumes.1 Reduced hippocampal volume is one of the most consistent findings in schizophrenia research.2–4 Also, Previous research has reported differences in hippocampal volume and white matter integrity in young adolescents who report psychotic experiences.5,6 However there has been little longitudinal research to investigate the developmental trajectory of these regions in adolescence with an increased susceptibility to psychotic disorders.Aimsto investigate two-year longitudinal changes in hippocampal volume in a sample of adolescents who reported psychotic experiences relative to their peers. To investigate the role of presence of co-morbid DSM IV mental disorders and stressful life events in influencing hippocampal volume and study the differences in hippocampus volume between adolescents who were having persistent symptoms versus adolescents with remitting symptoms.MethodsA longitudinal case-control study of 50 community-based adolescents aged 13–16 years (25 with psychotic experiences and a matched sample of 25 without psychotic experiences), compared hippocampal volume. All participants were assessed at baseline and two years follow up. T1 weighted anatomical high-resolution imaging and high angular resolution diffusion imaging data were used to conduct quantitative anatomical volumetric evaluations of global hippocampal volume. Clinical interviews also provided information on psychotic experiences, co-morbid disorders and adverse life events.ResultsThere were significant differences in the Right and Left Whole hippocampus between PE and Control group at baseline and 2-year follow up (p≤ 0.05). There were significant differences between PE persist and Control group in the left and right whole hippocampus (p≤ 0.05).DiscussionThe differences identified in our study suggest that early hippocampal reductions, may play a role in increasing vulnerability to psychosis.

F178. NEUROANATOMICAL PROFILES OF TREATMENT-RESISTANCE IN PATIENTS WITH SCHIZOPHRENIA

BackgroundAbout 20 to 35% of patients with schizophrenia show partial or no response to standard first-line antipsychotic treatment and are thus believed to have treatment-resistant schizophrenia (TRS). Notably, the antipsychotic clozapine (CLZ) has been reported to have superior efficacy compared to other agents for the treatment of TRS. However, a subset of patients still do not respond to CLZ treatment and are thus considered to have ultra-treatment-resistant schizophrenia (UTRS). Overall, the pathophysiology associated with UTRS appears to be different than TRS, yet both remain elusive. In light of the unknown factors underlying UTRS and TRS, along with the widely reported structural alterations that exist in patients with schizophrenia, our study aimed to examine subcortical structure volumes and cortical thickness in patients with UTRS, patients with TRS responding to CLZ (henceforth, TRS), patients responding to a first-line antipsychotic (treatment non-resistant schizophrenia (TnRS)), and healthy controls (HC). We hypothesized that deficits in subcortical structure volumes and cortical thickness would exist within the UTRS group compared to other groups.MethodsAs of December 2017, the sample consisted of a total of 94 participants, including 24 patients with UTRS, 24 patients with TRS, 21 patients with TnRS, and 25 HCs. Participants underwent a 3-dimensional T1-weighted scan in a 3T MRI machine. The MAGeT-Brain segmentation algorithm was used to acquire volumes of the thalamus, striatum, globus pallidus, hippocampus, and amygdala. Cortical thickness was estimated using the CIVET processing pipeline. Total brain volume was obtained using the BEaST method. Group comparisons were performed using analyses of covariance and post-hoc comparisons.ResultsGroup volumetric differences were identified bilaterally within the thalamus, striatum, and globus pallidus (p<0.01). Post-hoc investigations revealed that bilateral thalamic volumes were smaller in the UTRS group compared to the HC group (p<0.01), bilateral striatal volumes were larger in the TnRS group compared to the UTRS and HC groups (p<0.01), and bilateral globus pallidus volumes were larger in the TnRS group compared to the HC group (p<0.01). No differences in hippocampal, amygdala, or total brain volume were observed. At a 5% false discovery rate, widespread cortical thinning was identified in both the UTRS and TRS groups compared to the TnRS and HC groups; this effect was stronger and more diffuse in the UTRS group.DiscussionOur findings suggest that thalamic volume deficits might be a distinct feature of UTRS. Contrastingly, striatal and globus pallidus volume enlargement may be associated with first-line antipsychotic response or treatment. Cortical thinning is apparent in both the UTRS and TRS groups. In many cases, structural compromise appears to follow a continuum of response, whereby deficits are most severe in UTRS patients, followed by TRS patients, who are followed by TnRS patients and HCs.

Hippocampal subfield segmentation in temporal lobe epilepsy: Relation to outcomes.

ObjectiveTo investigate the clinical and surgical outcome correlates of preoperative hippocampal subfield volumes in patients with refractory temporal lobe epilepsy (TLE) using a new magnetic resonance imaging (MRI) multisequence segmentation technique.MethodsWe recruited 106 patients with TLE and hippocampal sclerosis (HS) who underwent conventional T1‐weighted and T2 short TI inversion recovery MRI. An automated hippocampal segmentation algorithm was used to identify twelve subfields in each hippocampus. A total of 76 patients underwent amygdalohippocampectomy and postoperative seizure outcome assessment using the standardized ILAE classification. Semiquantitative hippocampal internal architecture (HIA) ratings were correlated with hippocampal subfield volumes.ResultsPatients with left TLE had smaller volumes of the contralateral presubiculum and hippocampus‐amygdala transition area compared to those with right TLE. Patients with right TLE had reduced contralateral hippocampal tail volumes and improved outcomes. In all patients, there were no significant relationships between hippocampal subfield volumes and clinical variables such as duration and age at onset of epilepsy. There were no significant differences in any hippocampal subfield volumes between patients who were rendered seizure free and those with persistent postoperative seizure symptoms. Ipsilateral but not contralateral HIA ratings were significantly correlated with gross hippocampal and subfield volumes.ConclusionsOur results suggest that ipsilateral hippocampal subfield volumes are not related to the chronicity/severity of TLE. We did not find any hippocampal subfield volume or HIA rating differences in patients with optimal and unfavorable outcomes. In patients with TLE and HS, sophisticated analysis of hippocampal architecture on MRI may have limited value for prediction of postoperative outcome.

Hippocampal subfield volumes in children and adolescents with mood disorders

The hippocampus has been implicated in various mood disorders, with global volume deficits consistently found in patient populations. The hippocampus, however, consists of anatomically distinct subfields, and examination of specific subfield differences may elucidate the possible molecular mechanisms behind psychiatric pathologies. Indeed, adult studies have reported smaller hippocampal subfield volumes in regions within the cornu ammonis (CA1 and CA4), dentate gyrus (DG), and hippocampal tails in both patients with Major Depressive Disorder (MDD) and Bipolar Disorder (BD) compared to healthy controls. Subfield differences in pediatric patients with mood disorders, on the other hand, have not been extensively investigated. In the current study, magnetic resonance imaging scans were acquired for 141 children and adolescents between the ages of eight and eighteen (57 with BD, 30 with MDD, and 54 healthy controls). An automated segmentation method was then used to assess differences in hippocampal subfield volumes. Children and adolescents with BD were found to have significantly smaller volumes in the right CA1, CA4, and right subiculum, as well as the bilateral granule cell layer (GCL), molecular layer (ML), and hippocampal tails. The volume of the right subiculum in BD patients was also found to be negatively correlated with illness duration. Overall, the findings from this cross-sectional study provide evidence for specific hippocampal subfield volume differences in children and adolescents with BD compared to healthy controls and suggest progressive reductions with increased illness duration.

Spatial Cognition and Range Use in Free-Range Laying Hens.

Simple SummaryIndividual free-range laying hens vary in their use of the outdoor range. The outdoor environment is typically more complex and variable than indoor housing and thus range use may be related to differences in spatial abilities. Individual adult hens that never went outside were slower to learn a T-maze task—which requires birds to repeatedly find a food reward in one arm of the maze, compared to outdoor-preferring hens. Pullets that were faster to learn the maze also showed more visits to the range in their first month of range access but only in one of two tested groups. Early enrichment improved learning of the maze but only when the birds were tested before onset of lay. Fear may play a role in inhibiting bird’s spatial learning and their range use. More studies of different enriched rearing treatments and their impacts on fear and learning would be needed to confirm these findings. Overall, these results contribute to our understanding of why some birds choose to never access the outdoor range area.Radio-frequency identification tracking shows individual free-range laying hens vary in range use, with some never going outdoors. The range is typically more environmentally complex, requiring navigation to return to the indoor resources. Outdoor-preferring hens may have improved spatial abilities compared to indoor-preferring hens. Experiment 1 tested 32 adult ISA Brown hens in a T-maze learning task that showed exclusively-indoor birds were slowest to reach the learning success criterion (p < 0.05). Experiment 2 tested 117 pullets from enriched or non-enriched early rearing treatments (1 pen replicate per treatment) in the same maze at 15–16 or 17–18 weeks. Enriched birds reached learning success criterion faster at 15–16 weeks (p < 0.05) but not at 17–18 weeks (p > 0.05), the age that coincided with the onset of lay. Enriched birds that were faster to learn the maze task showed more range visits in the first 4 weeks of range access. Enriched and non-enriched birds showed no differences in telencephalon or hippocampal volume (p > 0.05). Fear may reduce spatial abilities but further testing with more pen replicates per early rearing treatments would improve our understanding of the relationship between spatial cognitive abilities and range use.

Subcortical volumetric differences between clinical stages of young people with affective and psychotic disorders

The aim of this study was to investigate differences in subcortical and hippocampal volumes between healthy controls, young people at an early stage of affective and psychotic disorders and those in more advanced stages, to identify markers associated with functional outcomes and illness severity. Young people presenting to youth mental health services with admixtures of depressive, manic and psychotic symptoms (n = 141), and healthy counterparts (n = 49), aged 18–25 were recruited. Participants underwent magnetic resonance imaging, clinical assessments and were rated as to their current clinical stage. Eighty-four patients were classified at the attenuated syndrome stage (Stage 1b) and 57 were classified as having discrete and persistent disorders (Stage 2+). Automated segmentation was performed using NeuroQuant® to determine volumes of subcortical and hippocampus structures which were compared between groups and correlated with clinical and functional outcomes. Compared to healthy controls, Stage 2+ patients showed significantly reduced right amygdala volumes. Whereas Stage 1b patients showed significantly reduced left caudate volumes compared to healthy controls. Smaller left caudate volume correlated with greater psychological distress and impaired functioning. This study shows a clinical application for an automated program to identify and track subcortical changes evident in young people with emerging psychopathology.

Association between hippocampus volume and symptom profiles in obsessive-compulsive disorder.

BackgroundThe hippocampus has recently been identified to play a key role in the pathophysiology of adult obsessive-compulsive disorder (OCD). Surprisingly, there is only limited evidence regarding the potential relationships with symptom dimensions. Due to the heterogeneity of symptoms in OCD, we aimed at further examining, whether hippocampal volume differences might be related to symptom profiles instead of single symptom dimensions.MethodsIn order to find out more about the potential association between clinical symptom profiles and alterations in hippocampal volume we categorized a large sample of OCD patients (N = 66) into distinct symptom profile groups using K-means clustering. In addition, hippocampal volumes of the different symptom profile groups were compared with hippocampal volumes in a sample of 66 healthy controls.ResultsWe found significant differences in hippocampal volume between the different symptom profile groups which remained significant after correcting for age, sex, total intracranial volume, OCI-total score, depression, medication, disease duration and scanner. The patient group characterized by overall lower symptom scores and without high symptom severity in any specific domain showed the highest hippocampal volume. Finally, the comparison with healthy controls demonstrated significantly lower hippocampal volumes in those patients whose symptom profile was characterized by a high severity of ordering and checking symptoms.ConclusionsPresent results provide further confirmation for alterations in hippocampus structure in OCD and suggest that symptom profiles which take into account the multi-symptomatic character of the disorder should be given greater attention in this context.

A Subset of Dogs with Presumptive Idiopathic Epilepsy Show Hippocampal Asymmetry: A Volumetric Comparison with Non-Epileptic Dogs Using MRI.

MRI-acquired volumetric measurements from 100 dogs with presumptive idiopathic epilepsy (IE) and 41 non-epileptic (non-IE) dogs were used to determine if hippocampal asymmetry exists in the IE as compared to the non-IE dogs. MRI databases from three institutions were searched for dogs that underwent MRI of the brain and were determined to have IE and those that were considered non-IE dogs. Volumes of the right and left hippocampi were measured using Mimics® software. Median hippocampal volumes of IE and non-IE dogs were 0.47 and 0.53 cm3, respectively. There was no significant difference in overall hippocampal volume between IE and non-IE dogs; however, IE dogs had greater hippocampal asymmetry than non-IE dogs (P < 0.012). A threshold value of 1.16 from the hippocampal ratio had an 85% specificity for identifying IE-associated asymmetry. Thirty five percent of IE dogs had a hippocampal ratio >1.16. Asymmetry was not associated with any particular hemisphere (P = 0.67). Our study indicates that hippocampal asymmetry occurs in a subset of dogs with presumptive idiopathic/genetic epilepsy, suggesting a structural etiology to some cases of IE.

Structural Co-Variance Patterns in Migraine: A Cross-Sectional Study Exploring the Role of the Hippocampus.

To interrogate hippocampal morphology and structural co-variance patterns in migraine patients and to investigate whether structural co-variance patterns relate to migraine disease characteristics. Migraine is associated with structural alterations in widespread cortical and subcortical regions associated with the sensory, cognitive, and affective components of pain processing. Recent studies have shown that migraine patients have differences in hippocampal structure and function relative to healthy control subjects, but whether hippocampal structure relates to disease characteristics including frequency of attacks, years lived with migraine and symptoms of allodynia remains unknown. Furthermore, this study investigated hippocampal volume co-variance patterns in migraineurs, an indirect measure of brain network connectivity. Here, we explore differences in hippocampal volume and structural co-variance patterns in migraine patients relative to healthy controls and examine whether these hippocampal measures relate to migraine disease burden. This study included 61 migraine patients and 57 healthy control subjects (healthy controls: median age = 34.0, IQR = 19.0; migraine patients: median age = 35.0, IQR = 17.5; P = .65). Regional brain volumes were automatically calculated using FreeSurfer version 5.3. Symptoms of allodynia were determined using the Allodynia Symptom Checklist 12 (ASC-12). Structural co-variance patterns were interrogated using pairwise correlations and group differences in correlation strength were estimated using Euclidian distance. A stepwise regression was used to investigate the relationship between structural co-variance patterns with migraine burden. Migraine patients had less left hippocampal volume (healthy controls: left hippocampal volume = 4276.8mm3 , SD = 425.3mm3 , migraine patients: left hippocampal volume = 4089.5mm3 , SD = 453.9mm3 , P = .02) and less total (right plus left) hippocampal volume (healthy controls: total hippocampal volume= 8690.8mm3 , SD = 855.1mm3 ; migraine patients: total hippocampal volume = 8341.8mm3 , SD = 917.9mm3 ; P = .03) compared to healthy controls. Migraineurs had stronger structural covariance between the hippocampi and cortico-limbic regions in the frontal lobe (inferior opercular gyrus), temporal lobe (planum temporale, amygdala), parietal lobe (angular gyrus, precuneus), and the cerebellar white matter. Results of a stepwise regression showed that hippocampal volumes and the interactions between hippocampal volumes with the volumes of other cortico-limbic regions associate with migraine-related allodynia but not with headache frequency or years lived with migraine. Migraineurs have less hippocampal volume and stronger hippocampal-cortico-limbic connectivity compared to healthy controls. Hippocampal volumes and measures of hippocampal volume connectivity with other cortico-limbic network regions associate with symptoms of allodynia.

A Pilot Study of Reduced Olfactory Bulb Volume as a Marker of PTSD in Childhood Trauma-Exposed Adult HIV-Infected Patients.

Evidence suggests that olfactory bulb (OB), a key structure in odor processing, may also be involved in mechanisms of traumatic stress. In animals, chronic stress reduces OB plasticity, and olfactory bulbectomy results in stress-enhanced startle reflex and autonomic dysregulation. However, OB morphometry has not been adequately studied in the development of stress disorders following childhood trauma in humans. The researchers conducted a pilot study evaluating the relationships between OB volume, childhood trauma, and lifetime posttraumatic stress disorder (PTSD) in a sample of 16 HIV-positive individuals, 13 of whom were exposed to childhood trauma of 9 developed PTSD. Participants were recruited from a larger cohort of inner city-dwelling HIV-positive populations in Washington, DC. Mean OB volumes were significantly reduced when PTSD and non-PTSD groups were compared, p = .019, as well as when trauma-exposed PTSD-positive and trauma-exposed PTSD-negative groups were compared, p = .008. No significant difference was observed when trauma-exposed and nonexposed participants were compared. The association between PTSD and right OB volume remained strong p = 0.002 after adjusting for group differences in sex, age, depression, hippocampal volume, and total intracranial volume. Because this study is limited by small sample size, further elucidation of relationships between OB, trauma, and PTSD should be investigated in larger cross-sectional and prospective studies and in diverse cohorts.

Cryptic sexual dimorphism in spatial memory and hippocampal oxytocin receptors in prairie voles (Microtus ochrogaster)

Sex differences are well documented and are conventionally associated with intense sex-specific selection. For example, spatial memory is frequently better in males, presumably due to males' tendency to navigate large spaces to find mates. Alternatively, monogamy (in which sex-specific selection is relatively relaxed) should diminish or eliminate differences in spatial ability and the mechanisms associated with this behavior. Nevertheless, phenotypic differences between monogamous males and females persist, sometimes cryptically. We hypothesize that sex-specific cognitive demands are present in monogamous species that will influence neural and behavioral phenotypes. The effects of these demands should be observable in spatial learning performance and neural structures associated with spatial learning and memory. We analyzed spatial memory performance, hippocampal volume and cell density, and hippocampal oxytocin receptor (OTR) expression in the socially monogamous prairie vole. Compared to females, males performed better in a spatial memory and spatial learning test. Although we found no sex difference in hippocampal volume or cell density, male OTR density was significantly lower than females, suggesting that performance may be regulated by sub-cellular mechanisms within the hippocampus that are less obvious than classic neuroanatomical features. Our results suggest an expanded role for oxytocin beyond facilitating social interactions, which may function in part to integrate social and spatial information.

Distinct Trajectories of Cortisol Response to Prolonged Acute Stress Are Linked to Affective Responses and Hippocampal Gray Matter Volume in Healthy Females.

The development of robust laboratory procedures for acute stress induction over the last decades has greatly advanced our understanding of stress responses in humans and their underlying neurobiological mechanisms. Nevertheless, attempts to uncover linear relationships among endocrine, neural, and affective responses to stress have generally yielded inconsistent results. Here, 79 healthy females completed a well established laboratory procedure of acute stress induction that was modified to prolong its effect. Endocrinological and subjective affect assessments revealed stress-induced increases in cortisol release and negative affect that persisted 65 and 100 min after stress onset, respectively, confirming a relatively prolonged acute stress induction. Applying latent class linear mixed modeling on individuals' patterns of cortisol responses identified three distinct trajectories of cortisol response: the hyper-response (n = 10), moderate-response (n = 21), and mild-response (n = 48) groups. Notably, whereas all three groups exhibited a significant stress-induced increase in cortisol release and negative affect, the hyper-response and mild-response groups both reported more negative affect relative to the moderate-response group. Structural MRI revealed no group differences in hippocampal and amygdala volumes, yet a continuous measure of cortisol response (area under the curve) showed that high and low levels of stress-induced cortisol release were associated with less hippocampal gray matter volume compared with moderate cortisol release. Together, these results suggest that distinct trajectories of cortisol response to prolonged acute stress among healthy females may not be captured by conventional linear analyses; instead, quadratic relations may better describe links between cortisol response to stress and affective responses, as well as hippocampal structural variability.SIGNIFICANCE STATEMENT Despite substantial research, it is unclear whether and how individual neuroendocrine stress response patterns are linked to affective responses to stress and structural variability in neuroendocrine regulatory brain regions. By applying latent class linear mixed modeling on individuals' patterns of cortisol responses to a prolonged acute stressor, we identified three distinct trajectories of cortisol response. Relative to the group showing a moderate cortisol response, groups characterized by hyper and mild cortisol response were both associated with more negative affect. Moreover, a continuous measure of cortisol response showed that high and low levels of stress-induced cortisol release correlated with reduced hippocampal gray matter volume. Given that neuroendocrine stress responses are conceptualized as biomarkers of stress susceptibility, these insights may have clinical implications.