The role of hippocampal subfield volume and fornix microstructure in episodic memory across the lifespan

Advancing age is associated with both declines in episodic memory and degradation of medial temporal lobe (MTL) structure. The contribution of MTL to episodic memory is complex and depends upon the interplay among hippocampal subfields and surrounding structures that participate in anatomical connectivity to the cortex through inputs (parahippocampal and entorhinal cortices) and outputs (fornix). However, the differential contributions of MTL system components in mediating age effects on memory remain unclear. In a sample of 177 healthy individuals aged 20–94 we collected high‐resolution T1‐weighted, ultrahigh‐resolution T2/PD, and diffusion tensor imaging (DTI) MRI sequences on a 3T Phillips Achieva scanner. Hippocampal subfield and entorhinal cortex (ERC) volumes were measured from T2/PD scans using a combination of manual tracings and training of a semiautomated pipeline. Parahippocampal gyrus volume was estimated using Freesurfer and DTI scans were used to obtain diffusion metrics from tractography of the fornix. Item and associative episodic memory constructs were formed from multiple tests. Competing structural equation models estimating differential association among these structural variables were specified and tested to investigate whether and how fornix diffusion and volume of parahippocampal gyrus, ERC, and hippocampal subfields mediate age effects on associative and/or item memory. The most parsimonious, best‐fitting model included an anatomically based path through the MTL as well as a single hippocampal construct which combined all subfields. Results indicated that fornix microstructure independently mediated the effect of age on associative memory, but not item memory. Additionally, all regions and estimated paths (including fornix) combined to significantly mediate the age‐associative memory relationship. These findings suggest that preservation of fornix connectivity and MTL structure with aging is important for maintenance of associative memory performance across the lifespan.     

Mapping the structural and functional network architecture of the medial temporal lobe using 7T MRI

Medial temporal lobe (MTL) subregions play integral roles in memory function and are differentially affected in various neurological and psychiatric disorders. The ability to structurally and functionally characterize these subregions may be important to understanding MTL physiology and diagnosing diseases involving the MTL. In this study, we characterized network architecture of the MTL in healthy subjects (n = 31) using both resting state functional MRI and MTL‐focused T2‐weighted structural MRI at 7 tesla. Ten MTL subregions per hemisphere, including hippocampal subfields and cortical regions of the parahippocampal gyrus, were segmented for each subject using a multi‐atlas algorithm. Both structural covariance matrices from correlations of subregion volumes across subjects, and functional connectivity matrices from correlations between subregion BOLD time series were generated. We found a moderate structural and strong functional inter‐hemispheric symmetry. Several bilateral hippocampal subregions (CA1, dentate gyrus, and subiculum) emerged as functional network hubs. We also observed that the structural and functional networks naturally separated into two modules closely corresponding to (a) bilateral hippocampal formations, and (b) bilateral extra‐hippocampal structures. Finally, we found a significant correlation in structural and functional connectivity (r = 0.25). Our findings represent a comprehensive analysis of network topology of the MTL at the subregion level. We share our data, methods, and findings as a reference for imaging methods and disease‐based research.     

Age‐related alterations in functional connectivity along the longitudinal axis of the hippocampus and its subfields

Hippocampal circuit alterations that differentially affect hippocampal subfields are associated with age‐related memory decline. Additionally, functional organization along the longitudinal axis of the hippocampus has revealed distinctions between anterior and posterior (A‐P) connectivity. Here, we examined the functional connectivity (FC) differences between young and older adults at high‐resolution within the medial temporal lobe network (entorhinal, perirhinal, and parahippocampal cortices), allowing us to explore how hippocampal subfield connectivity across the longitudinal axis of the hippocampus changes with age. Overall, we found reliably greater connectivity for younger adults than older adults between the hippocampus and parahippocampal cortex (PHC) and perirhinal cortex (PRC). This drop in functional connectivity was more pronounced in the anterior regions of the hippocampus than the posterior ones, consistent for each of the hippocampal subfields. Further, intra‐hippocampal connectivity also reflected an age‐related decrease in functional connectivity within the anterior hippocampus in older adults that was offset by an increase in posterior hippocampal functional connectivity. Interestingly, the anterior–posterior dysfunction in older adults between hippocampus and PHC was predictive of lure discrimination performance on the Mnemonic similarity task (MST), suggesting a role in memory performance. While age‐related dysfunction within the hippocampal subfields has been well‐documented, these results suggest that the age‐related dysfunction in hippocampal connectivity across the longitudinal axis may also contribute significantly to memory decline in older adults.     

Structural and functional correlates of behavioral pattern separation in the hippocampus and medial temporal lobe

Structures of the medial temporal lobe (MTL) are known to be involved in declarative memory processes. However, little is known about how age‐related changes in MTL structures, white matter integrity, and functional connectivity affect pattern separation processes in the MTL. In this study, we used magnetic resonance imaging (MRI) to measure the volumes of MTL regions of interest, including hippocampal subfields (dentate gyrus, CA3, CA1, and subiculum) in healthy older and younger adults. Additionally, we used diffusion tensor imaging to measure white matter integrity for both groups. Finally, we used functional MRI to acquire resting functional connectivity measures for both groups. We show that, along with age, the volume of left CA3/dentate gyrus predicts memory performance. Differences in fractional anisotropy and the strength of resting functional connections between the hippocampus and other cortical structures implicated in memory processing were not significant predictors of performance. As previous studies have only hinted, it seems that the size of left CA3/dentate gyrus contributes more to successful discrimination between similar mnemonic representations than other hippocampal sub‐fields, MTL structures, and other neuroimaging correlates. Accordingly, the implications of aging and atrophy on lure discrimination capacities are discussed. © 2014 Wiley Periodicals, Inc.     

Differential connectivity of perirhinal and parahippocampal cortices within human hippocampal subregions revealed by high-resolution functional imaging

Numerous studies support the importance of the perirhinal cortex (PRC) and parahippocampal cortex (PHC) in episodic memory. Theories of PRC and PHC function in humans have been informed by neuroanatomical studies of these regions obtained in animal tract-tracing studies, but knowledge of the connectivity of PHC and PRC in humans is limited. To address this issue, we used resting-state functional magnetic resonance imaging to compare the intrinsic functional connectivity profiles associated with the PRC and PHC both across the neocortex and within the subfields of the hippocampus. In Experiment 1, we acquired standard-resolution whole-brain resting-state fMRI data in 15 participants, and in Experiment 2, we acquired high-resolution resting-state fMRI data targeting the hippocampus in an independent sample of 15 participants. Experiment 1 revealed that PRC showed preferential connectivity with the anterior hippocampus, whereas PHC showed preferential connectivity with posterior hippocampus. Experiment 2 indicated that this anterior-posterior functional connectivity dissociation was more evident for subfields CA1 and subiculum than for a combined CA2/CA3/dentate gyrus region. Finally, whole-brain analyses from Experiment 1 revealed preferential PRC connectivity with an anterior temporal and frontal cortical network, and preferential PHC connectivity with a posterior medial temporal, parietal, and occipital network. These results suggest a framework for refining models of the functional organization of the human medial temporal lobes in which the PRC and PHC are associated with distinct neocortical pathways that, in turn, may differentially interact with regions along the anterior-posterior axis of the hippocampus.     

Structural and functional asymmetry of medial temporal subregions in unilateral temporal lobe epilepsy: A 7T MRI study

Mesial temporal lobe epilepsy (TLE) is a common neurological disorder affecting the hippocampus and surrounding medial temporal lobe (MTL). Although prior studies have analyzed whole‐brain network distortions in TLE patients, the functional network architecture of the MTL at the subregion level has not been examined. In this study, we utilized high‐resolution 7T T2‐weighted magnetic resonance imaging (MRI) and resting‐state BOLD‐fMRI to characterize volumetric asymmetry and functional network asymmetry of MTL subregions in unilateral medically refractory TLE patients and healthy controls. We subdivided the TLE group into mesial temporal sclerosis patients (TLE‐MTS) and MRI‐negative nonlesional patients (TLE‐NL). Using an automated multi‐atlas segmentation pipeline, we delineated 10 MTL subregions per hemisphere for each subject. We found significantly different patterns of volumetric asymmetry between the two groups, with TLE‐MTS exhibiting volumetric asymmetry corresponding to decreased volumes ipsilaterally in all hippocampal subfields, and TLE‐NL exhibiting no significant volumetric asymmetries other than a mild decrease in whole‐hippocampal volume ipsilaterally. We also found significantly different patterns of functional network asymmetry in the CA1 subfield and whole hippocampus, with TLE‐NL patients exhibiting asymmetry corresponding to increased connectivity ipsilaterally and TLE‐MTS patients exhibiting asymmetry corresponding to decreased connectivity ipsilaterally. Our findings provide initial evidence that functional neuroimaging‐based network properties within the MTL can distinguish between TLE subtypes. High‐resolution MRI has potential to improve localization of underlying brain network disruptions in TLE patients who are candidates for surgical resection.     

Hippocampal structural and functional changes associated with electroconvulsive therapy response

Previous animal models and structural imaging investigations have linked hippocampal neuroplasticity to electroconvulsive therapy (ECT) response, but the relationship between changes in hippocampal volume and temporal coherence in the context of ECT response is unknown. We hypothesized that ECT response would increase both hippocampal resting-state functional magnetic resonance imaging connectivity and hippocampal volumes. Patients with major depressive disorder (n=19) were scanned before and after the ECT series. Healthy, demographically matched comparisons (n=20) were scanned at one-time interval. Longitudinal changes in functional connectivity of hippocampal regions and volumes of hippocampal subfields were compared with reductions in ratings of depressive symptoms. Right hippocampal connectivity increased (normalized) after the ECT series and correlated with depressive symptom reduction. Similarly, the volumes of the right hippocampal cornu ammonis (CA2/3), dentate gyrus and subiculum regions increased, but the hippocampal subfields were unchanged relative to the comparison group. Connectivity changes were not evident in the left hippocampus, and volume changes were limited to the left CA2/3 subfields. The laterality of the right hippocampal functional connectivity and volume increases may be related to stimulus delivery method, which was predominately right unilateral in this investigation. The findings suggested that increased hippocampal functional connectivity and volumes may be biomarkers for ECT response.     

Functional connectivity along the anterior–posterior axis of hippocampal subfields in the ageing human brain

While age‐related volumetric changes in human hippocampal subfields have been reported, little is known about patterns of subfield functional connectivity (FC) in the context of healthy ageing. Here we investigated age‐related changes in patterns of FC down the anterior–posterior axis of each subfield. Using high resolution structural MRI we delineated the dentate gyrus (DG), CA fields (including separating DG from CA3), the subiculum, pre/parasubiculum, and the uncus in healthy young and older adults. We then used high resolution resting state functional MRI to measure FC in each group and to directly compare them. We first examined the FC of each subfield in its entirety, in terms of FC with other subfields and with neighboring cortical regions, namely, entorhinal, perirhinal, posterior parahippocampal, and retrosplenial cortices. Next, we analyzed subfield to subfield FC within different portions along the hippocampal anterior–posterior axis, and FC of each subfield portion with the neighboring cortical regions of interest. In general, the FC of the older adults was similar to that observed in the younger adults. We found that, as in the young group, the older group displayed intrinsic FC between the subfields that aligned with the tri‐synaptic circuit but also extended beyond it, and that FC between the subfields and neighboring cortical areas differed markedly along the anterior–posterior axis of each subfield. We observed only one significant difference between the young and older groups. Compared to the young group, the older participants had significantly reduced FC between the anterior CA1‐subiculum transition region and the transentorhinal cortex, two brain regions known to be disproportionately affected during the early stages of age‐related tau accumulation. Overall, these results contribute to ongoing efforts to characterize human hippocampal subfield connectivity, with implications for understanding hippocampal function and its modulation in the ageing brain.     

Material Specificity Drives Medial Temporal Lobe Familiarity But Not Hippocampal Recollection

The specific role of the perirhinal (PRC), entorhinal (ERC) and parahippocampal cortices (PHC) in supporting familiarity‐based recognition remains unknown. An fMRI study explored whether these medial temporal lobe (MTL) structures responded in the same way or differentially to familiarity as a function of stimulus type at recognition. A secondary aim was to explore whether the hippocampus responds in the same way to equally strong familiarity and recollection and whether this is influenced by the kind of stimulus involved. Univariate and multivariate analyses revealed that familiarity responses in the PRC, ERC, PHC and the amygdala are material‐specific. Specifically, the PRC and ERC selectively responded to object familiarity, while the PHC responded to both object and scene familiarity. The amygdala only responded to familiarity memory for faces. The hippocampus did not respond to stimulus familiarity for any of the three types of stimuli, but it did respond to recollection for all three types of stimuli. This was true even when recollection was contrasted to equally accurate familiarity. Overall, the findings suggest that the role of the MTL neocortices and the amygdala in familiarity‐based recognition depends on the kind of stimulus in memory, whereas the role of the hippocampus in recollection is independent of the type of cuing stimulus. © 2016 The Authors Hippocampus Published by Wiley Periodicals, Inc.     

Intrinsic connectivity of hippocampal subfields in normal elderly and mild cognitive impairment patients

Hippocampal connectivity has been widely described but connectivity specificities of hippocampal subfields and their changes in early AD are poorly known. The aim of this study was to highlight hippocampal subfield networks in healthy elderly (HE) and their changes in amnestic patients with mild cognitive impairment (aMCI). Thirty‐six HE and 27 aMCI patients underwent resting‐state functional MRI scans. Specific intrinsic connectivity of bilateral CA1, SUB (subiculum), and CA2/3/4/DG was identified in HE (using seeds derived from manually delineation on high‐resolution scans) and compared between HE and aMCI. Compared to the other subfields, CA1 was more strongly connected to the amygdala and occipital regions, CA2/3/4/DG to the left anterior cingulate cortex, temporal, and occipital regions, and SUB to the angular, precuneus, putamen, posterior cingulate, and frontal regions. aMCI patients showed reduced connectivity within the SUB network (with frontal and posterior cingulate regions). Our study highlighted for the first time three specific and distinct hippocampal subfield functional networks in HE, and their alterations in aMCI. These findings are important to understand AD specificities in both cognitive deficits and lesion topography, given the role of functional connectivity in these processes. Hum Brain Mapp 38:4922–4932, 2017. © 2017 Wiley Periodicals, Inc.     

Contributions of the hippocampal subfields and entorhinal cortex to disambiguation during working memory

The hippocampus and medial temporal lobes (MTL) support the successful formation of new memories without succumbing to interference from related, older memories. Computational models and animal findings have implicated the dentate gyrus (DG), CA3, CA1, and entorhinal cortex (EC) in the disambiguation and encoding of well‐established, episodic events that share common elements. However, it is unknown if these hippocampal subfields and MTL (entorhinal, perirhinal, parahippocampal) cortices also contribute during working memory when overlapping stimuli that share related features are rapidly encoded and subsequently maintained over a brief temporal delay. We hypothesized that activity in CA3/DG hippocampal subfields would be greater for the rapid encoding of stimuli with overlapping features than for the rapid encoding of stimuli with distinct features. In addition, we predicted that CA1 and EC, regions that are associated with creating long‐term episodic representations, would show greater sustained activity across both encoding and delay periods for representations of stimuli with overlapping features than for those with distinct features. We used high‐resolution fMRI during a delayed matching‐to‐sample (DMS) task using face pairs that either shared (overlapping condition, OL) or did not share (non‐overlapping condition, NOL) common elements. We contrasted the OL condition with the NOL condition separately at sample (encoding) and during a brief delay (maintenance). At sample, we observed activity localized to CA3/DG, the subiculum, and CA1. At delay, we observed activity localized to the subiculum and CA1 and activity within the entorhinal, perirhinal, and parahippocampal cortices. Our findings are consistent with our hypotheses and suggest that CA3/DG, CA1 and the subiculum support the disambiguation and encoding of overlapping representations while CA1, subiculum and entorhinal cortex maintain these overlapping representations during working memory. © 2013 Wiley Periodicals, Inc.     

The parahippocampal gyrus links the default‐mode cortical network with the medial temporal lobe memory system

The default‐mode network (DMN) is a distributed functional‐anatomic network implicated in supporting memory. Current resting‐state functional connectivity studies in humans remain divided on the exact involvement of medial temporal lobe (MTL) in this network at rest. Notably, it is unclear to what extent the MTL regions involved in successful memory encoding are connected to the cortical nodes of the DMN during resting state. Our findings using functional connectivity MRI analyses of resting‐state data indicate that the parahippocampal gyrus (PHG) is the primary hub of the DMN in the MTL during resting state. Also, connectivity of the PHG is distinct from connectivity of hippocampal regions identified by an associative memory‐encoding task. We confirmed that several hippocampal encoding regions lack significant functional connectivity with cortical DMN nodes during resting state. Additionally, a mediation analysis showed that resting‐state connectivity between the hippocampus and posterior cingulate cortex—a major hub of the DMN—is indirect and mediated by the PHG. Our findings support the hypothesis that the MTL memory system represents a functional subnetwork that relates to the cortical nodes of the DMN through parahippocampal functional connections. Hum Brain Mapp 35:1061–1073, 2014. © 2013 Wiley Periodicals, Inc.     

Regional vulnerability of hippocampal subfields to aging measured by structural and diffusion MRI

In the past few years, there has been an increasing awareness of the regional vulnerability of the hippocampus to age‐related processes. However, to date, no studies have assessed the effects of age on different structural magnetic resonance parameters in the specific hippocampal subfields. In this study, we measured volume, mean diffusivity (MD) and fractional anisotropy (FA) in the presubiculum, subiculum, fimbria, cornu ammonis (CA) 1,2‐3,4‐DG and the whole hippocampus in fifty cognitively intact elder adults between 50 and 75 years of age (20 men, 30 women). Segmentation of hippocampal subfields was performed using FreeSurfer. Individual MD and FA images were coregistered to T1‐weighted volumes using FLIRT of FSL. Linear regression analyses were performed to assess the effects of age on the anatomical measures of each subfield. In addition, multiple regression analyses were also carried out to assess which of the anatomical measures that showed a correlation with age in the previous analyses, were the best age predictors in the hippocampus. In agreement with previous studies, our results showed a significant association between age and volume (P < 0.001) as well as MD (P < 0.001) in the whole hippocampus. Regarding the specific hippocampal subfields, we found that age had a significant negative effect on volume in CA2‐3 (P < 0.001) and CA4‐DG (P < 0.001). Importantly, we found a positive effect of age on MD in CA2‐3 (P < 0.001) and fimbria (P < 0.001) as well as a negative age effect on FA in the subiculum (P < 0.001). Multiple regression analyses revealed that the best overall predictors of age in the hippocampus were MD in the fimbria and volume of CA2‐3, which explained 73.8% of the age variance. These results indicate that age has an effect both on volume and diffusion tensor imaging measures in different subfields, suggesting they provide complementary information on age‐related processes in the hippocampus. © 2013 Wiley Periodicals, Inc.     

Subfield atrophy pattern in temporal lobe epilepsy with and without mesial sclerosis detected by high-resolution MRI at 4 Tesla: Preliminary results

Purpose:   High-resolution magnetic resonance imaging (MRI) at 4 Tesla depicts details of the internal structure of the hippocampus not visible at 1.5 Tesla, and so allows for in vivo parcellation of different hippocampal subfields. The aim of this study was to test if distinct subfield atrophy patterns can be detected in temporal lobe epilepsy (TLE) with mesial temporal sclerosis (TLE-MTS) and without (TLE-no) hippocampal sclerosis.
Methods:   High-resolution T₂-weighted hippocampal images were acquired in 34 controls: 15 TLE-MTS and 18 TLE-no. Entorhinal cortex (ERC), subiculum (SUB), CA1, CA2, and CA3, and dentate (CA3&DG) volumes were determined using a manual parcellation scheme.
Results:   TLE-MTS had significantly smaller ipsilateral CA1, CA2, CA3&DG, and total hippocampal volume than controls or TLE-no. Mean ipsilateral CA1 and CA3&DG z-scores were significantly lower than ipsilateral CA2, ERC, and SUB z-scores. There were no significant differences between the various subfield or hippocampal z-scores on either the ipsi- or the contralateral side in TLE-no. Using a z-score ≤−2.0 to identify severe volume loss, the following atrophy patterns were found in TLE-MTS: CA1 atrophy, CA3&DG atrophy, CA1 and CA3&DG atrophy, and global hippocampal atrophy. Significant subfield atrophy was found in three TLE-no: contralateral SUB atrophy, bilateral CA3&DG atrophy, and ipsilateral ERC and SUB atrophy.
Discussion:   Using a manual parcellation scheme on 4 Tesla high-resolution MRI, we found the characteristic ipsilateral CA1 and CA3&DG atrophy described in TLE-MTS. Seventeen percent of the TLE-no had subfield atrophy despite normal total hippocampal volume. These findings indicate that high-resolution MRI and subfield volumetry provide superior information compared to standard hippocampal volumetry.     

Intact bilateral resting-state networks in the absence of the corpus callosum

Temporal correlations between different brain regions in the resting-state BOLD signal are thought to reflect intrinsic functional brain connectivity (Biswal et al., 1995; Greicius et al., 2003; Fox et al., 2007). The functional networks identified are typically bilaterally distributed across the cerebral hemispheres, show similarity to known white matter connections (Greicius et al., 2009), and are seen even in anesthetized monkeys (Vincent et al., 2007). Yet it remains unclear how they arise. Here we tested two distinct possibilities: (1) functional networks arise largely from structural connectivity constraints, and generally require direct interactions between functionally coupled regions mediated by white-matter tracts; and (2) functional networks emerge flexibly with the development of normal cognition and behavior and can be realized in multiple structural architectures. We conducted resting-state fMRI in eight adult humans with complete agenesis of the corpus callosum (AgCC) and normal intelligence, and compared their data to those from eight healthy matched controls. We performed three main analyses: anatomical region-of-interest-based correlations to test homotopic functional connectivity, independent component analysis (ICA) to reveal functional networks with a data-driven approach, and ICA-based interhemispheric correlation analysis. Both groups showed equivalently strong homotopic BOLD correlation. Surprisingly, almost all of the group-level independent components identified in controls were observed in AgCC and were predominantly bilaterally symmetric. The results argue that a normal complement of resting-state networks and intact functional coupling between the hemispheres can emerge in the absence of the corpus callosum, favoring the second over the first possibility listed above.     

Sex-related asymmetries in the morphology of the left and right hippocampi?

Cell densities were determined in left and right surgically removed hippocampal tissue of epileptic patients. Pyramidal cells were studied in CA1, CA4, and the dentate gyrus. Lower densities of nucleolated cells were found for males in the right CA1 and CA4 than on the left while there was no significant left-right difference in females. Moreover, we found a probable sex difference in intercorrelations of nucleolated cells among the three subfields. In males, they were positive and significant on the left while they were low on the right. In females, positive significant intercorrelations were obtained between some subfields and not between other subfields, on either side. The present findings suggest greater hippocampal lateralization in males than in females with higher hippocampal neuronal connectivity on the left in males than on the right.     

Hippocampal atrophy patterns in mild cognitive impairment and Alzheimer's disease

Background:

Histopathological studies and animal models suggest that hippocampal subfields may be differently affected by aging, Alzheimer's disease (AD), and other diseases. High‐resolution images at 4 Tesla depict details of the internal structure of the hippocampus allowing for in vivo volumetry of different subfields. The aims of this study were as follows: (1) to determine patterns of volume loss in hippocampal subfields in normal aging, AD, and amnestic mild cognitive impairment (MCI). (2) To determine if measurements of hippocampal subfields provide advantages over total hippocampal volume for differentiation between groups.

Methods:

Ninety‐one subjects (53 controls (mean age: 69.3 ± 7.3), 20 MCI (mean age: 73.6 ± 7.1), and 18 AD (mean age: 69.1 ± 9.5) were studied with a high‐resolution T2 weighted imaging sequence aimed at the hippocampus. Entorhinal cortex (ERC), subiculum, CA1, CA1‐CA2 transition zone (CA1‐2), CA3 & dentate gyrus (CA3&DG) were manually marked in the anterior third of the hippocampal body. Hippocampal volume was obtained from the Freesurfer and manually edited.

Results:

Compared to controls, AD had smaller volumes of ERC, subiculum, CA1, CA1‐2, and total hippocampal volumes. MCI had smaller CA1‐2 volumes. Discriminant analysis and power analysis showed that CA1‐2 was superior to total hippocampal volume for distinction between controls and MCI.

Conclusion:

The patterns of subfield atrophy in AD and MCI were consistent with patterns of neuronal cell loss/reduced synaptic density described by histopathology. These preliminary findings suggest that hippocampal subfield volumetry might be a better measure for diagnosis of early AD and for detection of other disease effects than measurement of total hippocampus. Hum Brain Mapp, 2010. © 2010 Wiley‐Liss, Inc.

     

Volumetric analysis of medial temporal lobe subregions in developmental amnesia using high‐resolution magnetic resonance imaging

There is great interest in the cognitive consequences of hippocampal volume loss in developmental amnesia (DA). In many DA cases, volume loss occurs before the hippocampus is fully developed, and yet little is known about the locus, extent, and distribution of damage in these cases. We used high‐resolution MRI to manually segment the medial temporal lobe (MTL) subregions in H.C., an adult with DA, and a group of sex‐, age‐ and education‐matched control participants (n = 10). The hippocampus was defined and divided into anterior (head) and posterior (body and tail) segments. Within the body of the hippocampus, the subregions (CA₁, DG/CA_2/3, and subiculum) were defined. Finally, the entorhinal (ERC), perirhinal (PRC), and parahippocampal (PHC) cortices were segmented. Anterior hippocampus was reduced bilaterally and posterior hippocampus was significantly reduced on the right. In the body of the hippocampus, all three subregions were reduced in the left hemisphere, whereas CA₁ and subiculum were reduced in the right hemisphere. No group differences were observed in the PRC and ERC, whereas left PHC volume was marginally increased in H.C. compared to controls. These results can be used to inform patterns of spared and impaired cognitive abilities in DA and perhaps in amnesia more generally. © The Authors. Hippocampus Published by Wiley Periodicals, Inc.     

Regional differentiation of cell densities in the left and right hippocampi of epileptic patients

Neuronal cell densities in surgically removed left or right hippocampal tissue of epileptic patients suffering from temporal lobe epilepsy were determined in CA1, CA4, and the dentate gyrus (DG). Mean densities showed no statistically significant left-right asymmetry in CA1 and the DG, consistent with findings by others. Mean densities did show previously unreported asymmetry in CA4; densities were significantly lower in the right CA4 than in the left. Another new finding is an asymmetry in regional intercorrelations: positive and significant correlations among the three subfields were obtained only in the left hippocampus. In addition, we confirmed previous findings of positive correlation between neuronal densities in CA1 and age of onset of habitual epilepsy, on either side. Taken together, the results suggest subtle left-right asymmetries in the vulnerability of the hippocampi to epilepsy-associated damage and/or higher neuronal connectivity or interdependence on the left than on the right.     

Hippocampal subfield alterations in pediatric patients with post-traumatic stress disorder

The hippocampus, a key structure with distinct subfield functions, is strongly implicated in the pathophysiology of post-traumatic stress disorder (PTSD); however, few studies of hippocampus subfields in PTSD have focused on pediatric patients. We therefore investigated the hippocampal subfield volume using an automated segmentation method and explored the subfield-centered functional connectivity aberrations related to the anatomical changes, in a homogenous population of traumatized children with and without PTSD. To investigate the potential diagnostic value in individual patients, we used a machine learning approach to identify features with significant discriminative power for diagnosis of PTSD using random forest classifiers. Compared to controls, we found significant mean volume reductions of 8.4% and 9.7% in the right presubiculum and hippocampal tail in patients, respectively. These two subfields’ volumes were the most significant contributors to group discrimination, with a mean classification accuracy of 69% and a specificity of 81%. These anatomical alterations, along with the altered functional connectivity between (pre)subiculum and inferior frontal gyrus, may underlie deficits in fear circuitry leading to dysfunction of fear extinction and episodic memory, causally important in post-traumatic symptoms such as hypervigilance and re-experience. For the first time, we suggest that hippocampal subfield volumes might be useful in discriminating traumatized children with and without PTSD.