Hippocampal Asymmetry Research Articles

Frequency Specificity of fMRI in Mesial Temporal Lobe Epilepsy.

Medial temporal lobe epilepsy (mTLE) is a system-level disease characterized by aberrant neuronal synchronization and widespread alterations in function. Previous studies have focused on the amplitude analysis of the blood oxygenation level-dependent (BOLD) signals to reveal the aberrant alterations in mTLE. However, these methods did not work well in the cases where the amplitudes of two oscillations are correlated but the underlying oscillations are neither phase coherent nor frequency consistent. To address this problem, we investigated the differences of frequency specificity between patients with mTLE and healthy controls using the extreme-point symmetric mode decomposition (ESMD) method. In this method, the BOLD signals were decomposed into a set of intrinsic mode functions (IMFs) and the instantaneous frequency of each IMF was calculated using the direct interpolation strategy. The intrinsic frequency (denoted as Freq) for every voxel was obtained by the weighted sum of the instantaneous frequencies of all the IMFs. The Freq was used as an index to evaluate the altered frequency specificity of 41 patients with mTLE (17 right-side, 24 left-side) and 24 healthy control subjects. The results show that the peak of frequency distribution curve for the patients moves towards the higher frequency than that for the healthy controls. Compared with the healthy control group, the patients with left mTLE demonstrate higher Freq in the default mode network, middle frontal gyrus, insula, middle temporal gyrus and calcarine gyrus; the patients with right mTLE demonstrate higher Freq in the precuneus and occipital lobe. For the three groups, the distinct frequency distribution appears in the left and right hippocampus due to the hippocampal structural and functional asymmetries. The preliminary results imply that the frequency-specific correlated oscillations in the distributed brain regions can provide information about the nature of diseases affecting the brain and the alterations of frequency specificity are associated with the pathological characteristics of mTLE.

PS166. Relationship of Hippocampal asymmetry and cognitive function in first-episode drug naïve major depressive disorder

PS166. Relationship of Hippocampal asymmetry and cognitive function in first-episode drug naïve major depressive disorder

Role of BDNF Val66Met functional polymorphism in temporal lobe epilepsy

Various studies suggested that brain-derived neurotrophic factor (BDNF) gene polymorphisms contributed to the development of many neurological disorders. However, whether BDNF Val66Met polymorphism is associated with epilepsy remains controversial. In our study, we tried to investigate the effects of this functional polymorphism on the occurrence of temporal lobe epilepsy (TLE) and its clinical phenotypes. Case-control studies were employed to study the association between BDNF Val66Met polymorphism and TLE, as well as its clinical phenotypes, and magnetic resonance imaging examinations and voxel-based morphometry analyses were carried out for further study. Our results showed that the frequency of Met allele was found to be lower in the TLE patients compared with the control subjects (43.9% vs. 48.6%, P = 0.012, OR = 1.21, 95% CI = 1.04–1.41), and the frequency of Met66 allele carriers in the TLE with hippocampal sclerosis was significantly lower than those non-carriers (20.5% vs. 29.1%, P = 0.040). However, we failed to find the difference between different genotypes and hippocampal asymmetry. Our findings suggested that BDNF Val66Met polymorphism might be correlated with epileptogenesis, and Met66 allele might play a protective role against the occurrence of TLE.

Functional and structural correlates of memory in patients with mesial temporal lobe epilepsy.

Individuals with medial temporal lobe epilepsy (mTLE) often show material-specific memory impairment (verbal for left, visuospatial for right hemisphere), which can be exacerbated following surgery aimed at the epileptogenic regions of medial and anterolateral temporal cortex. There is a growing body of evidence suggesting that characterization of structural and functional integrity of these regions using MRI can aid in prediction of post-surgical risk of further memory decline. We investigated the nature of the relationship between structural and functional indices of hippocampal integrity with pre-operative memory performance in a group of 26 patients with unilateral mTLE. Structural integrity was assessed using hippocampal volumes, while functional integrity was assessed using hippocampal activation during the encoding of novel scenes. We quantified structural and functional integrity in terms of asymmetry, calculated as (L − R)/(L + R). Factor scores for verbal and visual memory were calculated from a clinical database and an asymmetry score (verbal − visual) was used to characterize memory performance. We found, as expected, a significant difference between left and right mTLE (RTLE) groups for hippocampal volume asymmetry, with each group showing an asymmetry favoring the unaffected temporal lobe. Encoding activation asymmetry showed a similar pattern, with left mTLE patients showing activation preferential to the right hemisphere and RTLE patients showing the reverse. Finally, we demonstrated that functional integrity mediated the relationship between structural integrity and memory performance for memory asymmetry, suggesting that even if structural changes are evident, ultimately it is the functional integrity of the tissue that most closely explains behavioral performance.

Mesial Temporal Sclerosis: Accuracy of NeuroQuant versus Neuroradiologist.

We sought to compare the accuracy of a volumetric fully automated computer assessment of hippocampal volume asymmetry versus neuroradiologists' interpretations of the temporal lobes for mesial temporal sclerosis. Detecting mesial temporal sclerosis (MTS) is important for the evaluation of patients with temporal lobe epilepsy as it often guides surgical intervention. One feature of MTS is hippocampal volume loss. Electronic medical record and researcher reports of scans of patients with proved mesial temporal sclerosis were compared with volumetric assessment with an FDA-approved software package, NeuroQuant, for detection of mesial temporal sclerosis in 63 patients. The degree of volumetric asymmetry was analyzed to determine the neuroradiologists' threshold for detecting right-left asymmetry in temporal lobe volumes. Thirty-six patients had left-lateralized MTS, 25 had right-lateralized MTS, and 2 had bilateral MTS. The estimated accuracy of the neuroradiologist was 72.6% with a κ statistic of 0.512 (95% CI, 0.315-0.710) [moderate agreement, P < 3 × 10(-6)]), whereas the estimated accuracy of NeuroQuant was 79.4% with a κ statistic of 0.588 (95% CI, 0.388-0.787) [moderate agreement, P < 2 × 10(-6)]). This discrepancy in accuracy was not statistically significant. When at least a 5%-10% volume discrepancy between temporal lobes was present, the neuroradiologists detected it 75%-80% of the time. As a stand-alone fully automated software program that can process temporal lobe volume in 5-10 minutes, NeuroQuant compares favorably with trained neuroradiologists in predicting the side of mesial temporal sclerosis. Neuroradiologists can often detect even small temporal lobe volumetric changes visually.

Hippocampal asymmetry in angiotensin II modulatory effects on learning and memory in rats

Learning and memory effects of angiotensin II (Ang II) microinjected unilaterally (left or right) and bilaterally into hippocampal CA1 area on the background of the inhibited hippocampal angiotensin 1 receptors type (AT1) of male Wistar rats were studied. It was found that the combination (losartan 100 micrograms + Ang II 0.5 micrograms) microinjected bilaterally or into the left CA1 area improved learning and memory in shuttle-box and step through behavioral tests as compared to the respective controls. The effects were more pronounced after injection into the left CA1 area as compared to the right-side. These findings suggest thatAng II infused on the background of the inhibited CA1 hippocampal AT1 receptors ameliorated the cognitive processes. The data show also an asymmetric effect of Ang II on learning and memory processes in the hippocampus. The stronger modulating effect after microinjection of the combination (losartan + Ang II) into the left CA1 hippocampal area suggests a leftward bias in the rat. The results point to a differential distribution of angiotensin II receptors modulating the learning and memory processes in the left and right hippocampal CA1 area.

Hippocampal asymmetry is associated with cognitive decline in Type 2 diabetes

Hippocampal asymmetry is associated with cognitive decline in Type 2 diabetes

Automatic segmentation of the hippocampus for preterm neonates from early-in-life to term-equivalent age

IntroductionThe hippocampus, a medial temporal lobe structure central to learning and memory, is particularly vulnerable in preterm-born neonates. To date, segmentation of the hippocampus for preterm-born neonates has not yet been performed early-in-life (shortly after birth when clinically stable). The present study focuses on the development and validation of an automatic segmentation protocol that is based on the MAGeT-Brain (Multiple Automatically Generated Templates) algorithm to delineate the hippocampi of preterm neonates on their brain MRIs acquired at not only term-equivalent age but also early-in-life.MethodsFirst, we present a three-step manual segmentation protocol to delineate the hippocampus for preterm neonates and apply this protocol on 22 early-in-life and 22 term images. These manual segmentations are considered the gold standard in assessing the automatic segmentations. MAGeT-Brain, automatic hippocampal segmentation pipeline, requires only a small number of input atlases and reduces the registration and resampling errors by employing an intermediate template library. We assess the segmentation accuracy of MAGeT-Brain in three validation studies, evaluate the hippocampal growth from early-in-life to term-equivalent age, and study the effect of preterm birth on the hippocampal volume. The first experiment thoroughly validates MAGeT-Brain segmentation in three sets of 10-fold Monte Carlo cross-validation (MCCV) analyses with 187 different groups of input atlases and templates. The second experiment segments the neonatal hippocampi on 168 early-in-life and 154 term images and evaluates the hippocampal growth rate of 125 infants from early-in-life to term-equivalent age. The third experiment analyzes the effect of gestational age (GA) at birth on the average hippocampal volume at early-in-life and term-equivalent age using linear regression.ResultsThe final segmentations demonstrate that MAGeT-Brain consistently provides accurate segmentations in comparison to manually derived gold standards (mean Dice's Kappa > 0.79 and Euclidean distance <1.3 mm between centroids). Using this method, we demonstrate that the average volume of the hippocampus is significantly different (p < 0.0001) in early-in-life (621.8 mm3) and term-equivalent age (958.8 mm3). Using these differences, we generalize the hippocampal growth rate to 38.3 ± 11.7 mm3/week and 40.5 ± 12.9 mm3/week for the left and right hippocampi respectively. Not surprisingly, younger gestational age at birth is associated with smaller volumes of the hippocampi (p = 0.001).ConclusionsMAGeT-Brain is capable of segmenting hippocampi accurately in preterm neonates, even at early-in-life. Hippocampal asymmetry with a larger right side is demonstrated on early-in-life images, suggesting that this phenomenon has its onset in the 3rd trimester of gestation. Hippocampal volume assessed at the time of early-in-life and term-equivalent age is linearly associated with GA at birth, whereby smaller volumes are associated with earlier birth.

Magnetic resonance volumetry of the hippocampus in familial spontaneous epileptic cats

A strain of familial spontaneous epileptic cats (FSECs) with typical limbic seizures was identified in 2010. The electroencephalographic features suggested that an epileptogenic zone is present in the mesial temporal structures (i.e., amygdala and/or hippocampus). In this study, visual evaluations and quantitative analyses were performed by using 3D MR hippocampal volumetry in comparing FSECs with age-matched controls. Visual hippocampal asymmetries were seen in 8 of 14 (57.1%) FSECs. The FSEC group showed a significantly higher asymmetric ratio (4.15%) than the control group (0.99%). The smaller side of hippocampal volume (HV) (0.206 cm(3)) in FSECs was significantly smaller than the mean HV in controls (0.227 cm(3)). However, the means of left and right HVs and total HVs in FSECs showed no differences because the laterality of hippocampal atrophy was different in each individual. Therefore, since FSECs represent a true model of spontaneous epilepsy, hippocampal volumetry should be evaluated in each individual as well as in human patients. The significant asymmetry of HV suggests the potential for hippocampal atrophy in FSECs.

Delineation of hippocampal subregions using T1-weighted magnetic resonance images at 3Tesla.

Although several novel approaches for hippocampal subregion delineation have been developed, they need to be applied prospectively and may be limited by long scan times, the use of high field (>3T) imaging systems, and limited reliability metrics. Moreover, the majority of MR imaging data collected to date has employed a T1-weighted acquisition, creating a critical need for an approach that provides reliable hippocampal subregion segmentation using such a contrast. We present a highly reliable approach for the identification of six subregions comprising the hippocampal formation from MR images including the subiculum, dentate gyrus/cornu Ammonis 4 (DG/CA4), entorhinal cortex, fimbria, and anterior and posterior segments of cornu Ammonis 1-3 (CA1-3). MR images were obtained in the coronal plane using a standard 3D spoiled gradient sequence acquired on a GE 3T scanner through the whole head in approximately 10min. The average ICC for inter-rater reliability across right and left volumetric regions-of-interest was 0.85 (range 0.71-0.98, median 0.86) and the average ICC for intra-rater reliability was 0.92 (range 0.66-0.99, median 0.97). The mean Dice index for inter-rater reliability across right and left hemisphere subregions was 0.75 (range 0.70-0.81, median 0.75) and the mean Dice index for intra-rater reliability was 0.85 (range 0.82-0.90, median 0.85). An investigation of hippocampal asymmetry revealed significantly greater right compared to left hemisphere volumes in the anterior segment of CA1-3 and in the subiculum.

Hippocampal 5-HT1A receptor binding is related to object-location memory in humans.

Animal studies suggest that serotonin, mediated by the 5-HT1A receptor, plays a key role in spatial learning and memory. The role of serotonin in spatial memory in humans has, however, been less well studied. This study examined the relationship between serotonin receptor density in the human brain and spatial learning and memory using the 5-HT1A receptor ligand (18)F-4-(2'-methoxyphenyl)-1-[2'-(N-2-pyridinyl)-p-fluorobenzamido]-ethyl-piperazine ([(18)F] MPPF) and positron emission tomography (PET). Ten neurologically healthy individuals underwent two [(18)F] MPPF PET scans, one while performing a task which involves processing of high-level spatial information ('house scan'), and one while performing a task which involves processing of low-level spatial information ('tunnel scan'). Navigation, recall of arbitrary associations between objects and their spatial location, and ability to draw a plan of the environment were tested following the house scan. 5-HT1A receptor binding did not differ significantly between processing high and low levels of spatial information. Hippocampal asymmetry in [(18)F] MPPF binding, however, was associated with memory for object-location associations; lower right than left hippocampal binding potential (BPND) was related to better memory performance. We conclude that hippocampal serotonergic function plays a role in a fundamental component of human spatial memory, the ability to recall the location of encountered objects.

Neuropsychological measures of hippocampal function.

The role of the medial temporal lobe, specifically the hippocampus, in learning and memory has been consistently demonstrated over the past years and has led to the identification of the hippocampus as a target imaging marker for several neurological and psychiatric disorders. Hippocampal dysfunctions and smaller hippocampal volumes have been reported as characteristic for these disorders, and hippocampal asymmetry has been shown to be associated with memory deficits in older adults. These findings underline the importance of screenings for memory functions using neuropsychological cognitive test batteries within the clinical context. To the best of our knowledge, there has been no comprehensive review that has presented neuropsychological tests related to the hippocampus in detail. However, we did not aim to provide a complete overview of neuropsychological tests related to hippocampal function, which would fail in the light of the widespread area. This chapter focuses on neuropsychological tests that assess cognitive functions that depend on the hippocampus in a state-of-the-art fashion and additionally provide the link to several disorders for which hippocampal abnormalities are a common characteristic.

Molecular basis of chronic stress-induced hippocampal lateral asymmetry in rats and impact on learning and memory

Neurochemical lateralization has been demonstrated in the rat brain suggesting that such lateralization might contribute to behavior. Thus, the aim of the present study was to examine neurochemical asymmetry in the hippocampus, molecular basis of neurochemical lateralization and its impact on spatial learning and memory. Changes in noradrenaline content, tyrosine hydroxylase (TH) were studied in the right and left hippocampus of naive control and chronically isolated rats, by applying TaqMan RT-PCR and Western blot analysis. Hippocampal-based spatial learning and memory were evaluated using the Barnes maze. In control rats an asymmetrical right-left distribution of noradrenaline content and gene expression of catecholamine synthesizing enzyme was found. Chronic psychosocial stress further emphasized asymmetry. Isolation stress reduced noradrenaline content only in the right hippocampus. No changes were observed in gene expression and protein levels of TH in the right hippocampus, whereas expression of catecholamine synthesizing enzyme was elevated in the left hippocampus. Reduced noradrenaline content in the right hippocampus did not cause impairment in spatial learning and memory. Our findings suggest that chronic psychosocial stress reduces noradrenaline stores in the right hippocampus which may be caused by molecular asymmetry, but it does not affect spatial learning and memory.

The relationship between hippocampal asymmetry and temperament in adolescent borderline and antisocial personality pathology

Investigating etiological processes early in the life span represents an important step toward a better understanding of the development of personality pathology. The current study evaluated the interaction between an individual difference risk factor (i.e., temperament) and a biological risk factor for aggressive behavior (i.e., atypical [larger] rightward hippocampal asymmetry) in predicting the emergence of borderline personality disorder (BPD) and antisocial personality disorder symptoms during early adolescence. The sample consisted of 153 healthy adolescents (M = 12.6 years, SD = 0.4, range = 11.4-13.7) who were selected from a larger sample to maximize variation in temperament. Interactions between four temperament factors (effortful control, negative affectivity, surgency, and affiliativeness), based on the Early Adolescent Temperament Questionnaire-Revised, and volumetric measures of hippocampal asymmetry were examined as cross-sectional predictors of BPD and antisocial personality disorder symptoms. Boys were more likely to have elevated BPD symptoms if they were high on affiliation and had larger rightward hippocampal asymmetry. In boys, low affiliation was a significant predictor of BPD symptoms in the presence of low rightward hippocampal asymmetry. For girls, low effortful control was associated with elevated BPD symptoms in the presence of atypical rightward hippocampal asymmetry. This study builds on previous work reporting significant associations between atypical hippocampal asymmetry and poor behavioral regulation.

Measurement and genetics of human subcortical and hippocampal asymmetries in large datasets.

Functional and anatomical asymmetries are prevalent features of the human brain, linked to gender, handedness, and cognition. However, little is known about the neurodevelopmental processes involved. In zebrafish, asymmetries arise in the diencephalon before extending within the central nervous system. We aimed to identify genes involved in the development of subtle, left-right volumetric asymmetries of human subcortical structures using large datasets. We first tested the feasibility of measuring left-right volume differences in such large-scale samples, as assessed by two automated methods of subcortical segmentation (FSL|FIRST and FreeSurfer), using data from 235 subjects who had undergone MRI twice. We tested the agreement between the first and second scan, and the agreement between the segmentation methods, for measures of bilateral volumes of six subcortical structures and the hippocampus, and their volumetric asymmetries. We also tested whether there were biases introduced by left-right differences in the regional atlases used by the methods, by analyzing left-right flipped images. While many bilateral volumes were measured well (scan-rescan r = 0.6-0.8), most asymmetries, with the exception of the caudate nucleus, showed lower repeatabilites. We meta-analyzed genome-wide association scan results for caudate nucleus asymmetry in a combined sample of 3,028 adult subjects but did not detect associations at genome-wide significance (P < 5 × 10(-8) ). There was no enrichment of genetic association in genes involved in left-right patterning of the viscera. Our results provide important information for researchers who are currently aiming to carry out large-scale genome-wide studies of subcortical and hippocampal volumes, and their asymmetries.

APOE associated hemispheric asymmetry of entorhinal cortical thickness in aging and Alzheimer's disease

Across species structural and functional hemispheric asymmetry is a fundamental feature of the brain. Environmental and genetic factors determine this asymmetry during brain development and modulate its interaction with brain disorders. The e4 allele of the apolipoprotein E gene (APOE-4) is a risk factor for Alzheimer's disease, associated with regionally specific effects on brain morphology and function during the life span. Furthermore, entorhinal and hippocampal hemispheric asymmetry could be modified by pathology during Alzheimer's disease development. Using high-resolution magnetic resonance imaging and a cortical unfolding technique we investigated whether carrying the APOE-4 allele influences hemispheric asymmetry in the entorhinal cortex and the hippocampus among patients with Alzheimer's disease as well as in middle-aged and older cognitively healthy individuals. APOE-4 carriers showed a thinner entorhinal cortex in the left hemisphere when compared with the right hemisphere across all participants. Non-carriers of the allele showed this asymmetry only in the patient group. Cortical thickness in the hippocampus did not vary between hemispheres among APOE-4 allele carriers and non-carriers. The APOE-4 allele modulates hemispheric asymmetry in entorhinal cortical thickness. Among Alzheimer's disease patients, this asymmetry might be less dependent on the APOE genotype and a more general marker of incipient disease pathology.

Predictive value of hippocampal internal architecture asymmetry in temporal lobe epilepsy

Asymmetry of hippocampal internal architecture (HIA) clarity has been suggested to be a sign of hippocampal sclerosis (HS) and is frequently associated with other MRI findings of HS. The goal of this work is to use a previously developed HIA visual scoring system (Ver Hoef et al., 2013) to quantify HIA asymmetry in a retrospective series of consecutive temporal lobe epilepsy (TLE) patients and evaluate its value in predicting laterality of seizure onset both in patients with other signs of HS (HS+) and those without (HS-). The HIA scoring system was used to rate hippocampal asymmetry and to assess the agreement between HIA and seizure lateralization. The median values of the average HIA scores for each hippocampus were compared for HS+ epileptogenic hippocampi, HS- epileptogenic hippocampi, and non-epileptogenic hippocampi with a Kruskal-Wallis one-way analysis of variance by ranks. Pair-wise differences between groups were evaluated with the two-tailed Mann-Whitney U test. A logistic regression model examined the utility of average HIA asymmetry score in predicting the true laterality of seizure onset as determined by video-EEG. Sensitivity and specificity are calculated using various asymmetry thresholds in each patient group. Fifty-five patients were identified who met inclusion criteria. Thirteen patients (24%) were found to have hippocampal atrophy and/or signal abnormality indicative of HS (HS+) and 42 did not (HS-). Significant differences were observed in the distribution of individual and average HIA scores between each of the groups of hippocampi, with HS+ hippocampi having the lowest HIA scores and non-epileptogenic hippocampi having the highest. Logistic regression analysis showed that the average HIA asymmetry score was a strong predictor of the laterality of seizure onset (β=3.93508, p<0.001). HIA asymmetry remained significant even after adjustment for HS+/HS- status (β=3.8854, p<0.001). Among HS- patients, when the average HIA asymmetry score was equal to or exceeded a threshold value of 0.5, the specificity for correctly predicting the side of seizure onset was between 95% and 100% with a sensitivity of 40-45%. Among HS+ patients, a threshold of 0.3 yielded a sensitivity of 85% and specificity of 100%. In this report we show for the first time that HIA asymmetry is a significant predictor of the laterality of seizure onset in TLE patients with otherwise normal MRI findings, and that the proposed HIA scoring system has high specificity and moderate sensitivity for lateralizing seizure onset in patients with TLE.

Alzheimer's disease can be accurately differentiated from semantic dementia using automated measurement of hippocampal asymmetry

Alzheimer's disease can be accurately differentiated from semantic dementia using automated measurement of hippocampal asymmetry

Hippocampal Asymmetry: Differences in Structures and Functions

The structural asymmetry of bilateral hippocampus in mammals has been well recognized. Recent findings highlighted the accompanying functional asymmetries, as well as the molecular differences of the hippocampus. The present paper summarized these recent advances in understanding the hippocampal asymmetries at molecular, circuit and functional levels. Additionally, the addition of new neurons to the hippocampal circuit during adulthood is asymmetrical. We conclude that these differences in molecules and structures of bilateral hippocampus determined the variances in functionality between the two sides.

The relationship between Hippocampal asymmetry and working memory processing in combat-related PTSD - a monozygotic twin study.

BackgroundPTSD is associated with reduction in hippocampal volume and abnormalities in hippocampal function. Hippocampal asymmetry has received less attention, but potentially could indicate lateralised differences in vulnerability to trauma. The P300 event-related potential component reflects the immediate processing of significant environmental stimuli and has generators in several brain regions including the hippocampus. P300 amplitude is generally reduced in people with PTSD.MethodsOur study examined hippocampal volume asymmetry and the relationship between hippocampal asymmetry and P300 amplitude in male monozygotic twins discordant for Vietnam combat exposure. Lateralised hippocampal volume and P300 data were obtained from 70 male participants, of whom 12 had PTSD. We were able to compare (1) combat veterans with current PTSD; (2) their non-combat-exposed co-twins; (3) combat veterans without current PTSD and (4) their non-combat-exposed co-twins.ResultsThere were no significant differences between groups in hippocampal asymmetry. There were no group differences in performance of an auditory oddball target detection task or in P300 amplitude. There was a significant positive correlation between P300 amplitude and the magnitude of hippocampal asymmetry in participants with PTSD.ConclusionsThese findings suggest that greater hippocampal asymmetry in PTSD is associated with a need to allocate more attentional resources when processing significant environmental stimuli.