Total Hippocampus Research Articles

Decreased Oligodendrocyte and Neuron Number in Anterior Hippocampal Areas and the Entire Hippocampus in Schizophrenia: A Stereological Postmortem Study.

The hippocampus is involved in cognition as well as emotion, with deficits in both domains consistently described in schizophrenia. Moreover, the whole volumes of both the anterior and posterior region have been reported to be decreased in schizophrenia patients. While fewer oligodendrocyte numbers in the left and right cornu ammonis CA4 subregion of the posterior part of the hippocampus have been reported, the aim of this stereological study was to investigate cell numbers in either the dentate gyrus (DG) or subregions of the anterior hippocampus. In this design-based stereological study of the anterior part of the hippocampus comparing 10 patients with schizophrenia to 10 age- and gender-matched healthy controls were examined. Patients showed a decreased number of oligodendrocytes in the left CA4, fewer neurons in the left DG and smaller volumes in both the left CA4 and DG, which correlated with oligodendrocyte and neuron numbers, respectively. When exploring the total hippocampus, keeping previously published own results from the posterior part of the same brains in mind, both decreased oligodendrocyte numbers in the left CA4 and reduced volume remained significant. The decreased oligodendrocyte number speaks for a deficit in myelination and connectivity in schizophrenia which may originate from disturbed maturational processes. The reduced neuron number of the DG in the anterior hippocampus may well point to a reduced capacity of this region to produce new neurons up to adulthood. Both mechanisms may be involved in cognitive dysfunction in schizophrenia patients.

Preschool is a sensitive period for the influence of maternal support on the trajectory of hippocampal development

Building on well-established animal data demonstrating the effects of early maternal support on hippocampal development and adaptive coping, a few longitudinal studies suggest that early caregiver support also impacts human hippocampal development. How caregiving contributes to human hippocampal developmental trajectories, whether there are sensitive periods for these effects, as well as whether related variation in hippocampal development predicts later childhood emotion functioning are of major public health importance. The current study investigated these questions in a longitudinal study of preschoolers assessed annually for behavioral and emotional development, including observed caregiver support. One hundred and twenty-seven children participated in three waves of magnetic resonance brain imaging through school age and early adolescence. Multilevel modeling of the effects of preschool and school-age maternal support on hippocampal volumes across the three waves was conducted. Hippocampal volume increased faster for those with higher levels of preschool maternal support. Subjects with support 1 SD above the mean had a 2.06 times greater increase in total hippocampus volume across the three scans than those with 1 SD below the mean (2.70% vs. 1.31%). No effect of school-age support was found. Individual slopes of hippocampus volume were significantly associated with emotion regulation at scan 3. The findings demonstrate a significant effect of early childhood maternal support on hippocampal volume growth across school age and early adolescence and suggest an early childhood sensitive period for these effects. They also show that this growth trajectory is associated with later emotion functioning.

Abstract 06: Long-term Blood Pressure Variability Throughout Young Adulthood and Mid-life Cerebrovascular Structure and Function: The Coronary Artery Risk Development in Young Adults (CARDIA) Study

Introduction: In addition to average blood pressure (BP) values, BP variability has been suggested to be associated with lower cognitive function. It is unclear how long-term BP variability throughout young adulthood is associated with cerebrovascular structure (e.g., hippocampus) and function in midlife. Methods: Using data from the Coronary Artery Risk Development in Young Adults (CARDIA) study, which recruited healthy young adults ages 18 to 30 years (mean age 25 years) in 1985-1986, we assessed average BP over visits and visit-to visit BP variability (average real variability [ARV], defined as the absolute differences of BP between successive BP measurements) during 25-year follow-up (8 visits). Normal brain volume, abnormal brain volume, brain integrity assessed by fractional anisotropy, and cerebral blood flow were calculated by 3-Tesla MRI at the Year 25 follow-up (n=557, 52.2 % women, and 34.5 % African Americans). Results: For the 557 participants, mean ARV of SBP was 7.8±3.1 mm Hg. Higher ARV of SBP was associated with lower normal total brain volume, gray matter, and hippocampus after adjustment for covariates including intracranial volume and average BP during follow-up (Table). Higher average SBP during follow-up was associated with higher abnormal brain volume and lower integrity in the whole brain and the white matter, and lower blood flow in the hippocampus. Conclusions: Long-term visit-to-visit BP variability for 25 years beginning in young adulthood was associated with midlife cerebrovascular structural and functional alterations, independent of average BP during follow-up. Focusing not only on BP values alone but also on visit-to-visit BPV may be important to identify younger adults who may be at risk for developing lower cognitive function later.

Hippocampal subfield atrophy in relation to cerebrospinal fluid biomarkers and cognition in early Parkinson’s disease: a cross-sectional study

Cognition is often affected early in Parkinson’s disease (PD). Lewy body and amyloid β (Aβ) pathology and cortical atrophy may be involved. The aim of this study was to examine whether medial temporal lobe structural changes may be linked to cerebrospinal fluid (CSF) biomarker levels and cognition in early PD. PD patients had smaller volumes of total hippocampus, presubiculum, subiculum, CA2–3, CA4-DG, and hippocampal tail compared with normal controls (NCs). In the PD group, lower CSF Aβ38 and 42 were significant predictors for thinner perirhinal cortex. Lower Aβ42 and smaller presubiculum and subiculum predicted poorer verbal learning and delayed verbal recall. Smaller total hippocampus, presubiculum and subiculum predicted poorer visuospatial copying. Lower Aβ38 and 40 and thinner perirhinal cortex predicted poorer delayed visual reproduction. In conclusion, smaller volumes of hippocampal subfields and subhippocampal cortex thickness linked to lower CSF Aβ levels may contribute to cognitive impairment in early PD. Thirty-three early PD patients (13 without, 5 with subjective, and 15 with mild cognitive impairment) and NC had 3 T magnetic resonance imaging (MRI) scans. The MRI scans were post processed for volumes of hippocampal subfields and entorhinal and perirhinal cortical thickness. Lumbar puncture for CSF biomarkers Aβ38, 40, 42, total tau, phosphorylated tau (Innogenetics), and total α-synuclein (Meso Scale Diagnostics) were performed. Multiple regression analyses were used for between-group comparisons of the MRI measurements in the NC and PD groups and for assessment of CSF biomarkers and neuropsychological tests in relation to morphometry in the PD group.

Impact of neonatal anoxia on adult rat hippocampal volume, neurogenesis and behavior

Neonates that suffer oxygen deprivation during birth can have long lasting cognitive deficits, such as memory and learning impairments. Hippocampus, one of the main structures that participate in memory and learning processes, is a plastic and dynamic structure that conserves during life span the property of generating new cells which can become neurons, the so-called neurogenesis. The present study investigated whether a model of rat neonatal anoxia, that causes only respiratory distress, is able to alter the hippocampal volume, the neurogenesis rate and has functional implications in adult life. MRI analysis revealed significant hippocampal volume decrease in adult rats who had experienced neonatal anoxia compared to control animals for rostral, caudal and total hippocampus. In addition, these animals also had 55.7% decrease of double-labelled cells to BrdU and NeuN, reflecting a decrease in neurogenesis rate. Finally, behavioral analysis indicated that neonatal anoxia resulted in disruption of spatial working memory, similar to human condition, accompanied by an anxiogenic effect. The observed behavioral alterations caused by oxygen deprivation at birth might represent an outcome of the decreased hippocampal neurogenesis and volume, evidenced by immunohistochemistry and MRI analysis. Therefore, based on current findings we propose this model as suitable to explore new therapeutic approaches.

Association of Child Poverty, Brain Development, and Academic Achievement.

Children living in poverty generally perform poorly in school, with markedly lower standardized test scores and lower educational attainment. The longer children live in poverty, the greater their academic deficits. These patterns persist to adulthood, contributing to lifetime-reduced occupational attainment. To determine whether atypical patterns of structural brain development mediate the relationship between household poverty and impaired academic performance. Longitudinal cohort study analyzing 823 magnetic resonance imaging scans of 389 typically developing children and adolescents aged 4 to 22 years from the National Institutes of Health Magnetic Resonance Imaging Study of Normal Brain Development with complete sociodemographic and neuroimaging data. Data collection began in November 2001 and ended in August 2007. Participants were screened for a variety of factors suspected to adversely affect brain development, recruited at 6 data collection sites across the United States, assessed at baseline, and followed up at 24-month intervals for a total of 3 periods. Each study center used community-based sampling to reflect regional and overall US demographics of income, race, and ethnicity based on the US Department of Housing and Urban Development definitions of area income. One-quarter of sample households reported the total family income below 200% of the federal poverty level. Repeated observations were available for 301 participants. Household poverty measured by family income and adjusted for family size as a percentage of the federal poverty level. Children's scores on cognitive and academic achievement assessments and brain tissue, including gray matter of the total brain, frontal lobe, temporal lobe, and hippocampus. Poverty is tied to structural differences in several areas of the brain associated with school readiness skills, with the largest influence observed among children from the poorest households. Regional gray matter volumes of children below 1.5 times the federal poverty level were 3 to 4 percentage points below the developmental norm (P < .05). A larger gap of 8 to 10 percentage points was observed for children below the federal poverty level (P < .05). These developmental differences had consequences for children's academic achievement. On average, children from low-income households scored 4 to 7 points lower on standardized tests (P < .05). As much as 20% of the gap in test scores could be explained by maturational lags in the frontal and temporal lobes. The influence of poverty on children's learning and achievement is mediated by structural brain development. To avoid long-term costs of impaired academic functioning, households below 150% of the federal poverty level should be targeted for additional resources aimed at remediating early childhood environments.

Differential Atrophy of Hippocampal Subfields: A Comparative Study of Dementia with Lewy Bodies and Alzheimer Disease

Dementia with Lewy bodies (DLB) is characterized by relative preservation of the medial temporal lobe compared with Alzheimer disease (AD). The differential involvement of the hippocampal subfields in both diseases has not been clearly established, however. We aim to investigate hippocampal subfield differences invivo in a clinical cohort of DLB and AD subjects. 104 participants (35 DLBs, 36 ADs, and 35 healthy comparison [HC] subjects) underwent clinical assessment and 3T T1-weighted imaging. A Bayesian model implemented in Freesurfer was used to automatically segment the hippocampus and its subfields. We also examined associations between hippocampal subfields and tests of memory function. Both the AD and DLB groups demonstrated significant atrophy of the total hippocampus relative to HC but the DLB group was characterized by preservation of the cornu ammonis 1 (CA1), fimbria, and fissure. In contrast, all the hippocampal subfields except the fissure were significantly atrophied in AD compared with both DLB and HC groups. Among DLB subjects, CA1 was correlated with the Recent Memory score of the CAMCOG and Delayed Recall subscores of the HVLT. DLB is characterized by milder hippocampal atrophy that was accompanied by preservation of the CA1. The CA1 was also associated with memory function in DLB. Our findings highlight the promising role of hippocampal subfield volumetry, particularly that of the CA1, as a biomarker for the distinction between AD and DLB.

Brain atrophy and physical disability in primary progressive multiple sclerosis: A volumetric study.

Grey matter atrophy has been shown in primary progressive multiple sclerosis (PPMS), but its association with physical incapacity is unclear. We submitted 19 patients with PPMS to a neurological evaluation and brain magnetic resonance imaging (MRI) with volumetric analysis using FreeSurfer. We found no relation between the Expanded Disability Status Scale or disease duration and the grey matter or white matter structures analysed. Lesion load was negatively correlated with cortical and subcortical grey matter volumes, but not with total white matter volume. We concluded that physical disability in PPMS is not directly related to brain atrophy and that focal inflammatory white matter lesions may contribute to progressive neuronal degeneration. Primary progressive multiple sclerosis (PPMS) is characterized by chronic progression since onset, with predominant involvement of the spinal cord and prominent neurodegeneration. Grey matter atrophy has been shown in patients with PPMS, but its association with clinical incapacity is uncertain. We investigated the relationship between regional brain atrophy and physical disability in patients with PPMS. Patients with an established diagnosis of PPMS underwent a neurological evaluation followed by brain MRI at 1.5 T. Volumetric analysis was performed with FreeSurfer software, and evaluated the neocortex, total white matter, total subcortical grey matter, putamen, caudate, globus pallidus, thalamus, hippocampus, brainstem, corpus callosum and pre-central gyrus volumes. Clinical data obtained included physical disability as measured by the Expanded Disability Status Scale (EDSS). Nineteen patients were included, 14 female (73.7%), mean age of 55.7 (SD 7.6) and mean disease duration of 13.0 years (SD 8.8). Median EDSS score was 6.0 (3.5-8.0). The average T1 lesion load (4.9 cm³, SD 3.4) and T2 load (10.5 cm³, SD 9.9) did not relate to disease duration. There was no significant correlation between EDSS score or disease duration and the cortical grey matter, deep grey matter or white matter structures analysed. Lesion load was negatively correlated with cortical and subcortical grey matter volumes (p < 0.05), but not with total white matter volume. Physical disability in PPMS is not directly related to brain volume loss. Grey matter atrophy correlates with lesion load in patients with PPMS, indicating that focal inflammatory white matter lesions may contribute to progressive neuronal degeneration.

Neonatal hypoxia-ischemia induces attention-deficit hyperactivity disorder-like behavior in rats.

Attention-deficit hyperactivity disorder (ADHD) may be caused by genetic or environmental factors. Among environmental factors, perinatal complications are related, such as neonatal hypoxia-ischemia (HI). Thus, the aim of this study was to investigate whether HI contributes to the development of characteristics related to ADHD in adult rats, and to correlate the behavioral results with brain damage volume. Male Wistar rats were divided into 2 groups: HI and control. The HI procedure consisted of a permanent occlusion of the right common carotid artery followed by a period of hypoxia (90 min; 8% O₂ and 92% N₂) on the 7th postnatal day. Two months later, animals were evaluated in the open field test during a single 5-min session, and in the 5-choice serial reaction time task (5-CSRTT), over 25 weeks. Our results demonstrated that animals submitted to HI manifest cognitive impairments in task acquisition, deficits in sustained attention, and increases in impulsivity and compulsivity in response to task manipulation in the 5-CSRTT. Locomotor activity observed in open field did not differ between groups. Moreover, brain volume loss in the total hemisphere, cerebral cortex, white matter, hippocampus, and striatum were observed in HI animals, especially on the side ipsilateral to the lesion. From these results, we can infer that neonatal HI is an environmental factor that could contribute to the development of behavioral characteristics observed in ADHD that are associated with general brain atrophy.

Depressed suicide attempters have smaller hippocampus than depressed patients without suicide attempts

BackgroundDespite known relationship between hippocampal volumes and major depressive episodes (MDE) and the increased suicidality in MDE, the links between hippocampal volumes and suicidality remain unclear in major depressive disorders (MDD). If the hippocampus could be a biomarker of suicide attempts in depression, it could be useful for prevention matters. This study assessed the association between hippocampal volumes and suicide attempts in MDD. MethodsHippocampal volumes assessed with automatic segmentation were compared in 63 patients with MDD, with (n = 24) or without (n = 39) suicide attempts. Acute (<one month) and past (>one month) suicide attempts were studied. ResultsAlthough not different in terms of socio-demographic, MDD and MDE clinical features, suicide attempters had lower total hippocampus volumes than non-attempters (4.61 (±1.15) cm3 vs 5.22 (±0.99) cm3; w = 625.5; p = 0.03), especially for acute suicide attempts (4.19 (±0.81) cm3 vs 5.22 (±0.99) cm3; w = 334; p = 0.005), even after adjustment on brain volumes, sex, age, Hamilton Depression Rating Scale (HDRS) scores and MDD duration. A ROC analysis showed that a total hippocampal volume threshold of 5.00 cm3 had a 98.2% negative predictive value for acute suicide attempts. ConclusionDepressed suicide attempters have smaller hippocampus than depressed patients without suicide attempts, independently from socio-demographics and MDD characteristics. This difference is related to acute suicide attempts but neither to past suicide attempts nor to duration since the first suicide attempt, suggesting that hippocampal volume could be a suicidal state marker in MDE. Further studies are required to better understand this association.

Medial temporal lobe default mode functioning and hippocampal structure as vulnerability indicators for schizophrenia: A MRI study of non-psychotic adolescent first-degree relatives

BackgroundClues to the etiology and pathophysiology of schizophrenia can be examined in their first-degree relatives because they are genetically related to an ill family member, and have few confounds like medications. Brain abnormalities observed in young relatives are neurobiological indicators of vulnerability to illness. We examined the hypothesis that the hippocampus and parahippocampus are structurally abnormal and are related to default mode network (DMN) function and cognitive abnormalities in relatives of probands. MethodsSubjects were 27 non-psychotic, first-degree relatives of individuals diagnosed with schizophrenia, and 48 normal controls, ages 13 to 28, undergoing high-resolution magnetic resonance imaging (MRI) at 1.5T. After structural scan acquisition a subset of subjects performed 2-back working memory (WM) and 0-back tasks during functional MRI (fMRI) alternating with rest. fMRI data were analyzed using SPM-8. Volumes of total cerebrum, hippocampus, and parahippocampal gyrus were measured using semi-automated morphometry. ResultsCompared to controls, relatives had significantly smaller left hippocampi, without volumetric reduction in the parahippocampus. Relatives showed significantly less suppression of DMN activity in the left parahippocampal gyrus. Left hippocampal and posterior parahippocampal volumes were inversely and significantly associated with DMN processing (smaller volumes, less suppression) in relatives. Task suppression in parahippocampal gyrus significantly correlated with WM performance within the relatives. ConclusionResults support the hypothesis that the vulnerability to schizophrenia includes smaller hippocampi and DMN suppression deficits, and these are associated with poorer WM. Findings suggest a primary structural, neurodevelopmental, medial temporal lobe abnormality associated with altered DMN function independent of psychosis.

Peripheral antioxidant markers are associated with total hippocampal and CA3/dentate gyrus volume in MDD and healthy controls–preliminary findings

Several psychiatric disorders, including major depressive disorder (MDD), are associated with increased blood markers of oxidative stress. The relevance of this to the oxidation-sensitive hippocampus (HC) is unknown. We investigated the relationship between peripheral oxidative stress markers and HC volume in unmedicated individuals with MDD (n=16) and healthy controls (n=19). To conserve power, our primary analysis was carried out in the combined group of subjects, and secondary analyses examined each group separately. Oxidative stress markers (oxidized glutathione (GSSG)) and antioxidants (reduced glutathione (GSH), glutathione peroxidase (Gpx), and Vitamin C) were assessed, and a “total net antioxidant score” was calculated. 4-T MRI estimated total HC volume and HC subfield (CA1, CA1-CA2 transition zone, subiculum and CA3/dentate gyrus [CA3&DG]) volumes. Across groups, the antioxidant score was significantly and positively correlated with total HC volume and CA3&DG subfield volume (normalized to total intracranial volume), adjusting for age and sex. Similar relationships were observed in each individual group but missed statistical significance, likely due to type II errors, with the exception of a significant correlation between the antioxidant score and CA3&DG volume in the MDD group. These preliminary data are consistent with oxidative stress being associated with smaller total HC and CA3&DG subfield volumes.

CEREBRAL ATROPHY IN OLDER ADULTS WITH MILD COGNITIVE IMPAIRMENT WITH OR WITHOUT DEPRESSIVE SYMPTOMS AND IN PATIENTS WITH LATE-LIFE DEPRESSION

total of 15 rats with a mean age of 16.6 months were used for this study. Hippocampus volumes were computed using structural Magnetic ResonanceImaging (MRI). The images [18F]FDG were acquired using PET at baseline and follow-up. Then the percent change of FDG values were calculated with respect to the baseline values. Whole brain images were obtained by MRI using Fast Imaging with Steady State Precession. PET images were then correlated at a voxel level with the hippocampus volume from the MRI images. Results: In WT, average volumes in total brain and hippocampus (mm3) at baseline were 2418.91 6 142.68 and 78.76 6 5.98, respectively. In TG, average volume in total brain and hippocampus were 2390.31 6 210.00 and 81.686 8.28, respectively. In WT, average follow-up total brain volume and hippocampus were 2454.45 6 131.99 and 76.9875 6 2.67, respectively; and 2392.13 6 208.64 and 75.48 6 8.75, respectively in TG. Changes in FDG and hippocampal volume in WT were -0.72 6 6.7% and 5.3 6 5.0%, respectively and in TG were 6.1 6 11% and 6.2 6 3.4%, respectively. In WT, 6-month hypometabolism in frontal, temporal, cingulate cortex and striatum were associated with individual baseline hippocampal volumes. In TG, 6-month hypometabolism in the amygdala, basal forebrain, cingulate cortex and striatum were associated with individual baseline hippocampal volumes. Conclusions:While hippocampal volumes predict metabolic declines in fronto-cortical regions inWT, in TG carriers of brain amyloidosis, such associations predominate in limbic regions. These results support the vulnerability of limbic cortex to brain amyloidosis.

CAA IN MUTANT AD MICE: A COMPARATIVE STUDY TO HUMAN AD CASES

Changes of gross vascular morphology were reported for different mouse models of Alzheimer’s disease (AD) and for human AD cases. Those changes comprise cerebral amyloid angiopathy (CAA) but also increased IR area of vascular markers such as Collagen IV. The latter was interpreted as vascular sprouting and/or increase of vascular diameter. However, this interpretation is critical within two respects: A) Sprouting or diameter alteration are two totally different mechanisms to increase blood flow as a reaction to lacking nourishment as found in AD. Thus it is important to figure out, which one exactly is responsible for increased vascular marker signal. B) The translationability of findings in mouse models to human cases has to be investigated. Uniform systematic random sets of brain sections deriving a) from AD model APP SL transgenic (Tg) mice at three ages (months 6; 9 ;12) and b) from human AD cases* of three different Braak stages (Braak stages I/II; III/IV; V/VI) were immunohistochemically labeled for detection of amyloid (clone 6E10) and vessels (SMA, Collagen IV), imaged and quantitatively evaluated in terms of mean vascular diameter and percentage of amyloid related to vascular cross section area using image analysis software (Axio.Imager Z1 microscope, ImageProPlus). Sections of non-transgenic littermate mice (nTg) and age-matched non AD human subjects served as controls. In mice mean arterial cross sectional size was evaluated by manual delineation of smooth muscle actin (SMA, specific to arteries in the brain) labeling of 11 defined arteries in the cerebral cortex at three different lateral levels of the brain. Data are meta-data and derive from Tg and nTg vehicle controls of different studies. Since SMA did not label on human sections (formalin over-fixation and/or paraffin embedding), Collagen IV was used, which also labels to venules. This implies that unfortunately no direct comparable data to mean arterial size between mice and men could be. For collagen IV IR vasculature, samples of humans were evaluated by counting in stripes of a mean of 3 mm² imaged at 20x through white and grey matter in two sections per region and subject. Samples of human cingulate, temporal, frontal and occipital cortex were averaged and are shown in graphs as “cortex”. In mice values of four sections from five medio-lateral levels in a hemisphere were averaged to an individual mean for the total cerebral cortex and the total hippocampus (grey matter).

CHRONIC ANTIPSYCHOTIC MEDICATION EXPOSURE CHANGES THE BRAIN STRUCTURE IN MACAQUE MONKEYS

There is evidence that brain structure is abnormal in patients with bipolar disorder. Lithium intake appears to ׳normalise׳ global and local brain volumes, but effects of antipsychotic medication on brain volume or cortical thickness are less clear. Here, we aim to disentangle disease-specific brain deviations from those induced by antipsychotic medication and lithium intake using a large homogeneous sample of patients with bipolar disorder type I. Magnetic resonance imaging brain scans were obtained from 266 patients and 171 control subjects. Subcortical volumes and global and focal cortical measures (volume, thickness, and surface area) were compared between patients and controls. In patients, the association between lithium and antipsychotic medication intake and global, subcortical and cortical measures was investigated. Patients showed significantly larger lateral and third ventricles, smaller total brain, caudate nucleus, and pallidum volumes and thinner cortex in some small clusters in frontal, parietal and cingulate regions as compared with controls. Lithium-free patients had significantly smaller total brain, thalamus, putamen, pallidum, hippocampus and accumbens volumes compared to patients on lithium. In patients, use of antipsychotic medication was related to larger third ventricle and smaller hippocampus and supramarginal cortex volume. Patients with bipolar disorder show abnormalities in total brain, subcortical, and ventricle volume, particularly in the nucleus caudate and pallidum. Abnormalities in cortical thickness were scattered and clusters were relatively small. Lithium-free patients showed more pronounced abnormalities as compared with those on lithium. The associations between antipsychotic medication and brain volume are subtle and less pronounced than those of lithium.

Volumetric changes in hippocampal subregions and their relation to memory in pediatric nonlesional localization‐related epilepsy

Developmental differences in structure and function have been reported along the hippocampal subregions. The aims of this study were to determine if there were volumetric differences in hippocampal head (HH), body (HB), tail (HT), and total hippocampus (TotH)) in children with nonlesional localization-related epilepsy relative to controls, and the relation between hippocampal subregions with episodic memory and clinical parameters. Forty-eight children with nonlesional localization-related epilepsy, consisting of 29 left-sided and 19 right-sided epilepsy, and 27 healthy controls were recruited. All patients and controls underwent volumetric T1-weighted imaging, and verbal and nonverbal memory testing. The volume of hippocampal subregions was compared between patients and controls. The associations between left hippocampal subregions with verbal memory; right hippocampal subregions with nonverbal memory; and hippocampal subregions with age, age at seizure onset, and seizure frequency were assessed. Patients with left-sided epilepsy had smaller left HH (p=0.003) and HB (p=0.012), right HB (p=0.021) and HT (p=0.015), and right TotH (p=0.020) volumes. Those with right-sided epilepsy had smaller right HT (p=0.018) volume. There were no statistically significant differences between verbal and nonverbal memory in left-sided and right-sided epilepsy relative to controls (all p>0.025). In left-sided epilepsy, there was a significant association between left HH volume with verbal memory (β=0.492, p=0.001). There was no significant association between left and right hippocampal subregions with verbal and nonverbal memory, respectively, in right-sided epilepsy and controls (all p>0.002). In left-sided and right-sided epilepsy, there was no significant association between hippocampal subregions with age, age at seizure onset, and seizure frequency (all p>0.002). We have found hippocampal volume reduction, but did not identify a gradient in the severity of volume reduction along the hippocampal axis in children with localization-related epilepsy. Further study is needed to clarify if there are volumetric changes within the cornu ammonis subfields and dentate gyrus. A PowerPoint slide summarizing this article is available for download in the Supporting Information section here.

Subcortical Deep Gray Matter Pathology in Patients with Multiple Sclerosis Is Associated with White Matter Lesion Burden and Atrophy but Not with Cortical Atrophy: A Diffusion Tensor MRI Study

The association between subcortical deep gray matter, white matter, and cortical pathology is not well understood in MS. The aim of this study was to use DTI to investigate the subcortical deep gray matter alterations and their relationship with lesion burden, white matter, and cortical atrophy in patients with MS and healthy control patients. A total of 210 patients with relapsing-remitting MS, 75 patients with progressive MS, and 110 healthy control patients were included in the study. DTI metrics in whole brain, normal-appearing white matter, normal-appearing gray matter, and subcortical deep gray matter structures were compared. The association between DTI metrics of the subcortical deep gray matter structures with lesion burden, normalized white matter volume, and normalized cortical volume was investigated. DTI measures were significantly different in whole brain, normal-appearing white matter, and normal-appearing gray matter among the groups (P < .01). Significant differences in DTI diffusivity of total subcortical deep gray matter, caudate, thalamus, and hippocampus (P < .001) were found. DTI diffusivity of total subcortical deep gray matter was significantly associated with normalized white matter volume (P < .001) and normalized cortical volume (P = .033) in healthy control patients. In both relapsing and progressive MS groups, the DTI subcortical deep gray matter measures were associated with the lesion burden and with normalized white matter volume (P < .001), but not with normalized cortical volume. These findings suggest that subcortical deep gray matter abnormalities are associated with white matter lesion burden and atrophy, whereas cortical atrophy is not associated with microstructural alterations of subcortical deep gray matter structures in patients with MS.

Plasma tau as a window to the brain-negative associations with brain volume and memory function in mild cognitive impairment and early alzheimer's disease

Neurofibrillary tangles are associated with cognitive dysfunction, and hippocampal atrophy with increased CSF tau markers. However, the plasma tau levels of Alzheimer's disease (AD) have not been well studied. We investigated plasma tau by using an immunomagnetic reduction assay in 20 patients with mild cognitive impairment (MCI) due to AD, 10 early AD dementia, and 30 healthy elders (HE). All received a 3D-brain MRI scan and a set of cognitive function test. We explored their relationships with both brain structure and cognitive functions. Images were analyzed to determine the brain volumes and gray matter densities. Patients with MCI or early AD had significantly increased plasma tau levels compared with HE. Plasma tau levels were negatively associated with the performance of logical memory, visual reproduction, and verbal fluency; also negatively associated with volume of total gray matter, hippocampus, amygdala; and gray matter densities of various regions. Regression analyses indicated that logical memory explained 0.394 and hippocampus volume predicted .608 of the variance of plasma tau levels, both P < 0.001. Education years were negatively associated with the gray matter densities of the supramarginal (r = -0.407), middle temporal gyrus (r = -0.40) and precuneus (r = -0.377; all P < 0.05) in HE; and negatively associated with plasma tau levels in patients (r = -0.626). We propose that plasma tau may serve as a window to both structure and function of the brain. Higher education is a protective factor against AD and is associated with lower plasma tau levels in patients.

Hippocampal changes and associations with psychological symptoms in subjects suffering from anorexia nervosa

Background: Anorexia nervosa (AN) is one of the most and severe diseases with the highest mortality rate of all mental disorders. Individuals with AN show certain personality traits, which precede the onset of the disease, e.g. anxiety, obsessive behaviour, negative emotionality, inflexibility, and perfectionism. Studies found a reduction of total hippocampus–/INS;amygdala formation volume, a reduced volume in the parahippocampal gyrus bilaterally, and a hypoperfusion in the amygdala–/INS;hippocampus complex.

Interactive effects of chronic cigarette smoking and age on hippocampal volumes

BackgroundPrevious cross-sectional MRI studies with healthy, young-to-middle-aged adults reported no significant differences between smokers and non-smokers on total hippocampal volume. However, these studies did not specifically test for greater age-related volume loss in the total hippocampus or hippocampal subregions in smokers, and did they did not examine relationships between hippocampal and subfield volumes and episodic learning and memory performance. MethodsHealthy, young-to-middle-aged (45±12 years of age) smokers (n=39) and non-smokers (n=43) were compared on total hippocampal and subfield volumes derived from high-resolution 4Tesla MRI, emphasizing testing for greater age-related volume losses in smokers. Associations between hippocampal volumes and measures of episodic learning and memory were examined. ResultsSmokers showed significantly smaller volumes, as well as greater volume loss with increasing age than non-smokers in the bilateral total hippocampus and multiple subfields. In smokers, greater pack-years were associated with smaller volumes of the total hippocampus, presubiculum, and subiculum. In the entire cohort, performance on measures of learning and memory was related to larger total hippocampal and several subfield volumes, predominately in the left hemisphere. ConclusionsChronic cigarette smoking in this young-to-middle aged cohort was associated with smaller total hippocampal and subfield volumes, which were exacerbated by advancing age. Findings also indicated an adverse smoking dose/duration response (i.e., pack-years) with total hippocampal and select subfield volumes. These hippocampal volume abnormalities in smokers may be related to the deficiencies in episodic learning and memory in young-to-middle-aged smokers reported in previous studies.