MRI volumetry of the hippocampus, amygdala, entorhinal cortex, and perirhinal cortex after status epilepticus

Neuronal damage has been observed in the medial temporal lobe of both humans and animals following status epilepticus. The aim of the present study was to investigate the occurrence of medial temporal lobe damage in status epilepticus patients treated in hospital with a predetermined protocol and to assess whether the changes progress in a long-term follow-up. The volumes of the hippocampus, amygdala, entorhinal and perirhinal cortices were measured using magnetic resonance imaging (MRI) in nine adult patients with status epilepticus 3 weeks, 6 and 12 months after the insult. The control group included 20 healthy subjects. The etiology of status epilepticus was an acute process in one patient and a chronic process in eight cases. The mean duration of secondarily generalized tonic–clonic status epilepticus episodes was 1 h and 44 min. Volumetric MRI indicated that none of the patients developed marked volume reduction in the hippocampus, amygdala, or the entorhinal and perirhinal cortices during the 1-year follow-up period. Status epilepticus does not invariably lead to a progressive volume reduction in the medial temporal lobe structures of adult patients treated promptly in hospital with a predetermined protocol for rapid cessation of seizure activity.     

Perceptual and mnemonic matching-to-sample in humans: contributions of the hippocampus, perirhinal and other medial temporal lobe cortices

Two questions were addressed by the present study. The first was whether the previously reported item recognition deficit which is shown by amnesic patients may be due to a perceptual rather than a memory deficit. To address this question a group of amnesic patients were tested on a 14-choice forced-choice visual item recognition test which included a "simultaneous" condition in which the sample remained visible during the matching decision and a zero second delay. Eacott, Gaffan and Murray (1994) have reported an impairment in simultaneous matching-to-sample following perirhinal damage in monkeys. In our amnesic patients, a deficit was found only after filled delays of 10 seconds or longer and this was also the case for a subgroup of patients whose damage included the perirhinal cortex. The second question, which arose from the model of Aggleton and Brown (1999), was whether performance on the DMS task would remain intact following selective damage to the hippocampus. We tested a patient with bilateral damage to the hippocampus on the 14-choice DMS task and found that her performance was not significantly impaired at delays of up to 30 seconds.     

Impaired associative memory in temporal lobe epilepsy subjects after lesions of hippocampus, parahippocampal gyrus, and amygdala

There has been growing interest in the differential role of medial temporal lobe structures in learning and memory. The goal of the present study was to clarify how lesions of hippocampus, parahippocampal gyrus, and amygdala interfere with associative learning and memory. Thirty subjects with pharmacoresistant medial temporal lobe epilepsy (TLE) and temporal lobe removal were compared with 30 matched healthy control subjects. A set of neuropsychological test measures and an associative learning task requiring the learning and recall of objects and faces were administered. The lesions of hippocampus, parahippocampal gyrus, amygdala, and fusiform gyrus of TLE subjects were determined by three-dimensional magnetic resonance imaging (3-D MRI) volumetric assessment. The results indicate that TLE subjects with combined large hippocampal lesions, large parahippocampal gyrus (i.e., perirhinal/entorhinal) lesions, and large amygdala lesions learned and recalled the associative task significantly worse than control subjects or subjects with small lesions of the hippocampus, parahippocampal gyrus, and amygdala. Regression analysis revealed that larger lesions of the parahippocampal gyrus (i.e., perirhinal/entorhinal cortices) were significantly related to increasing deficits on the task, and that hippocampal and amygdala lesion size did not significantly improve the prediction. Our results suggest that perirhinal and entorhinal cortices may contribute predominantly to the associative learning and recall of objects and faces.     

Cortical efferents of the perirhinal,postrhinal, and entorhinal cortices of the rat

We investigated the cortical efferents of the parahippocampal region by placing injections of the anterograde tracers, Phaseolus vulgaris‐leuccoagglutinin, and biotinylated dextran amine, throughout the perirhinal (PER), postrhinal (POR), and entorhinal cortices of the rat brain. The resulting density of labeled fibers was evaluated in 25 subregions of the piriform, frontal, insular, temporal, cingulate, parietal, and occipital areas. The locations of labeled terminal fibers differed substantially depending on whether the location of the injection site was in PER area 35, PER area 36, POR, or the lateral or the medial entorhinal (LEA and MEA). The differences were greater for sensory regions. For example, the POR efferents preferentially target visual and spatial regions, whereas the PER efferents target all sensory modalities. The cortical efferents of each region largely reciprocate the cortical afferents, though the degree of reciprocity varied across originating and target regions. The laminar pattern of terminal fibers was consistent with the notion that the efferents are feedback projections. The density and amount of labeled fibers also differed substantially depending on the regional location of injection sites. PER area 36 and POR give rise to a greater number of heavy projections, followed by PER area 35. LEA also gives rise to widespread cortical efferents, arising mainly from a narrow band of cortex adjacent to the PER. In contrast, the remainder of the LEA and the MEA provides only weak efferents to cortical regions. Prior work has shown that nonspatial and spatial information is transmitted to the hippocampus via the PER‐LEA and POR‐MEA pathways, respectively. Our findings suggest that the return projections follow the same pathways, though perhaps with less segregration. © 2009 Wiley‐Liss, Inc.     

Cortical afferents of the perirhinal,postrhinal, and entorhinal cortices of the rat

We have divided the cortical regions surrounding the rat hippocampus into three cytoarchitectonically discrete cortical regions, the perirhinal, the postrhinal, and the entorhinal cortices. These regions appear to be homologous to the monkey perirhinal, parahippocampal, and entorhinal cortices, respectively. The origin of cortical afferents to these regions is well-documented in the monkey but less is known about them in the rat. The present study investigated the origins of cortical input to the rat perirhinal (areas 35 and 36) and postrhinal cortices and the lateral and medial subdivisions of the entorhinal cortex (LEA and MEA) by placing injections of retrograde tracers at several locations within each region. For each experiment, the total numbers of retrogradely labeled cells (and cell densities) were estimated for 34 cortical regions. We found that the complement of cortical inputs differs for each of the five regions. Area 35 receives its heaviest input from entorhinal, piriform, and insular areas. Area 36 receives its heaviest projections from other temporal cortical regions such as ventral temporal association cortex. Area 36 also receives substantial input from insular and entorhinal areas. Whereas area 36 receives similar magnitudes of input from cortices subserving all sensory modalities, the heaviest projections to the postrhinal cortex originate in visual associational cortex and visuospatial areas such as the posterior parietal cortex. The cortical projections to the LEA are heavier than to the MEA and differ in origin. The LEA is primarily innervated by the perirhinal, insular, piriform, and postrhinal cortices. The MEA is primarily innervated by the piriform and postrhinal cortices, but also receives minor projections from retrosplenial, posterior parietal, and visual association areas. J. Comp. Neurol. 398:179–205, 1998. © 1998 Wiley-Liss, Inc.     

A volumetric MRI study of the hippocampus and the parahippocampal region after unilateral medial temporal lobe resection

Segmentation guidelines on high-resolution MRI designed to assess remaining volumes of the hippocampus and the parahippocampal cortices after medial temporal lobe (MTL) surgery could provide a useful tool to investigate the involvement of these anatomical regions in surgical outcomes and in human memory. For this purpose, we implemented an MRI volumetric analysis, already applied to healthy population or epileptic patient before surgery, to quantify the volume of the hippocampus, the temporopolar cortex and the regions of the parahippocampal gyrus (perirhinal, entorhinal and parahippocampal cortices) spared after unilateral MTL resection carried out to treat medically uncontrolled temporal lobe epilepsy (TLE). Based on the locations of remaining anatomical landmarks, we quantified the volume of these regions in 24 patients after MTL resection and in 16 control participants. Our results show that (1) mean volumes of these regions contralateral to the epileptic focus were similar to those of normal subjects, (2) volumetric measures obtained from the resected side were much smaller than those from the non-resected side or from normal values and (3) the extent of MTL resection was comparable in right or left MTL surgery. Individual analysis of patients showed that the parahippocampal cortex, as opposed to the other regions, was not systematically removed across patients. As a post-operative MRI-based method, it therefore proves valuable to assess group data as well as to explore differences between individual patients.     

Distribution of calbindin D-28k in the entorhinal,perirhinal, and parahippocampal cortices of the macaque monkey

We examined the distribution of calbindin D-28k-immunoreactive (CB-IR) neurons, fibers, and neuropil in the entorhinal (area 28), perirhinal (areas 35 and 36), and parahippocampal (areas TH and TF) cortices in the macaque monkey. Two main findings are reported. First, except for CB-IR neurogliaform cells that are only observed in the parahippocampal cortex, the morphology of CB-stained pyramidal and nonpyramidal cells were similar across the three cortical areas examined. Second, we find that the topography of CB staining differed between the three areas. The entorhinal cortex exhibits the most striking gradient of CB staining such that the most anterior and medial portions are most strongly labeled, whereas posterior and lateral areas exhibit only weak labeling. The labeling throughout the perirhinal and parahippocampal cortices is more homogeneous. Area 35 contains only lightly stained neuropil and few CB-IR cells. Area 36 and areas TH and TF of the parahippocampal cortex contain a moderate to high density of CB-IR cells and fibers throughout their full rostrocaudal extents, although each area exhibits unique laminar patterns of staining. In all areas examined, the highest density of CB-positive cells and fibers is observed in superficial layers with lower densities of CB-positive cells and fibers present in deep layers. These findings, taken together with our current understanding of the connections of these areas may have implications for understanding the circuit properties of the entorhinal, perirhinal, and parahippocampal cortices areas in both normal and disease states.     

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.     

Common pathway in the medial temporal lobe for storage and recovery of words as revealed by event-related functional MRI

Lesion studies have provided compelling evidence that episodic memory is dependent on the integrity of the medial temporal lobe (MTL). This role of the MTL in episodic memory has been supported by several neuroimaging studies during both episodic encoding and retrieval. After two meta-analyses of positron emission tomography (PET) and functional magnetic resonance imaging (fMRI) studies, we investigated a possible dissociation within the MTL memory system in relation to encoding and retrieval processes. Based on previous reports that specifically related the function of the MTL in episodic memory to successful encoding and actual recovery of information, we applied event-related fMRI to compare successful encoding of words (ES) directly with successful recognition of those same words (RS). Our results did not indicate a clear dissociation between encoding and retrieval activations in the MTL. Instead, a region in the left MTL, covering the parahippocampal cortex and hippocampal formation, which was activated during ES almost completely overlapped with the area that was activated during RS. An additional region in the left anterior MTL, including the entorhinal cortex, was found to be activated exclusively during ES. Research has indicated that a large percentage of cells in this region are particularly sensitive to the relative novelty of stimuli. Our results, therefore, suggest that the parahippocampal/hippocampal region is involved in the formation and subsequent reactivation of memory traces, whereas the activity observed in the entorhinal cortex may reflect elementary memory processes related to novelty detection.     

Nitric oxide synthase and arginase in the rat hippocampus and the entorhinal, perirhinal, postrhinal, and temporal cortices: regional variations and age-related changes

Increasing evidence suggests that nitric oxide synthase (NOS)/nitric oxide (NO) contributes to the aging process. By contrast, the role of arginase, which shares a common substrate with NOS, has not been determined. In the present study, regional variations and age-related changes in NOS and arginase in the hippocampus and its neighboring structures were investigated for the first time. In young adult rats, high levels of NOS activity were found in the entorhinal, perirhinal, and postrhinal cortices, whereas low values were located in the hippocampus and the temporal cortex. Interestingly, arginase activity showed an overall inverse pattern with the lowest levels in the entorhinal and perirhinal cortices. When a comparison was carried out between young (4-month-old) and aged (24-month-old) rats, significant increases in total NOS activity were found in the aged entorhinal and temporal cortices, and a significant decrease in arginase activity was observed in the aged postrhinal cortex. Western blotting demonstrated significant decreases in both neuronal and endothelial NOS expression in the aged hippocampus and postrhinal cortex, whereas arginase I and II expression did not show age-related changes in any region examined. Activity and protein expression of inducible NOS were not detected in any tissue from either group. The present findings of region-specific changes in NOS and arginase appear to support the potential involvement of NOS/NO in the aging process and raise the issue of a possible contribution of arginase to aging.     

Cannabinoid CB1 receptor protein expression in the rat hippocampus and entorhinal,perirhinal, postrhinal and temporal cortices: regional variations and age-related changes

Cannabinoids have been shown to disrupt memory processes and these effects occur primarily through cannabinoid CB1 receptors in the brain. The present study investigates, for the first time, the regional variations and age-related changes in CB1 protein expression in the hippocampus and its neighbouring entorhinal, perirhinal, postrhinal and temporal cortices using Western blotting. In young adult rats, CB1 protein was highly expressed in the hippocampus and within the hippocampus, the greatest density of CB1 protein was located in CA1. When a comparison was made between young (4-month-old) and aged (24-month-old) rats, CB1 protein expression was significantly increased in the aged entorhinal and temporal cortices and was significantly decreased in the aged postrhinal cortex. The present study demonstrates region-specific changes in CB1 protein expression during ageing and further suggests that cannabinoid CB1 receptors may contribute to the aging process.     

The amygdala and temporal lobe simple partial seizures: a prospective and quantitative MRI study

PURPOSE: To determine whether specific temporal lobe simple partial seizures (SPSs) are associated with an abnormal amygdala T2 (AT2) ipsilateral to the seizure focus in patients with intractable unilateral temporal lobe epilepsy (TLE). AT2 relaxation time mapping is a sensitive method for the detection of abnormal tissue in the amygdala in patients with refractory TLE. The relation between an abnormal AT2 in the epileptic temporal lobe and amygdala seizure onset has not been established. METHODS: Fifty patients with intractable unilateral TLE and concordant data during presurgical evaluation were included. Patients with a foreign-tissue lesion on standard magnetic resonance imaging (MRI) were excluded. All had AT2 mapping. Fifteen types of SPSs were ascertained prospectively, systematically, and blinded to the results of AT2 mapping. The SPSs of patients with a normal AT2 (n = 25) were compared with those of patients with an abnormal AT2 ipsilateral to the seizure focus (n = 25). RESULTS: The group of patients with an abnormal AT2 reported a median of six types of SPSs (range 1-11), in comparison with a median of three types of SPSs (range, 0-7) for the group with a normal AT2 (p<0.01). Déjà vu, a warm sensation, an indescribable strange sensation, a cephalic sensation, and fear were associated with an abnormal AT2. The combination of déjà vu, a cephalic sensation, a warm sensation, a gustatory hallucination, and an indescribable strange sensation discriminated best between the 25 patients with a normal and the 25 patients with an abnormal AT2. CONCLUSIONS: A high number and the types of different SPSs provide clinical evidence for early involvement of the amygdala during seizures in patients with refractory unilateral TLE and an abnormal AT2 in the epileptic temporal lobe     

Visual association encoding activates the medial temporal lobe: A functional magnetic resonance imaging study

The involvement of structures in the medial temporal lobe during the encoding of visual associations was studied with functional magnetic resonance imaging. In 11 out of 12 normal healthy volunteers this task resulted in activation in posterior portions of the parahippocampal region, close to the collateral sulcus. In seven subjects activation was encountered in the hippocampal formation. The visual association task as adapted for this study may provide a sensitive measure to study anterograde amnesia prevalent in Alzheimer's disease. Therefore, the present paradigm enables the study of individual changes in learning and memory capacities over time. Hippocampus 1997;7:594–601. © 1997 Wiley-Liss, Inc.     

颞叶癫痫海马、杏仁核及皮层病灶的超微结构观察

对１９例临床确认为颞叶癫痫而行海马杏仁核及皮层病灶切除术棘波灶的标本进行了电镜观察，发现在病变神经元周围，有髓神经纤维髓板松解、融合，轴突出芽；无髓神经纤维内微丝、微管排列紊乱，缠绕成团，见团样小体结构；突触中圆形突触小泡增多或耗竭。扁平状突触小泡相对较少；神经毡及毛细血管旁可见许多颗粒性电子致密物沉着，经Ｘ射线显微分析排除无机离子，考虑这些沉着物仍为机体的有机成份。半定量观察结果显示三个部位超微病理变化具有相似性。本课题的观察提示神经纤维及突触的病变可能是痫性活动的直接形态依据，而这种具有病变神经纤维及突触的神经元在痫性活动中则可能起着“起搏细胞”的作用，痫性活动的产生与兴奋性及抑制性递质的平衡失调有关。     

Relationship of medial temporal lobe atrophy,APOE genotype,and cognitive reserve in preclinical Alzheimer's disease

This study evaluated the utility of baseline and longitudinal magnetic resonance imaging (MRI) measures of medial temporal lobe brain regions collected when participants were cognitively normal and largely in middle age (mean age 57 years) to predict the time to onset of clinical symptoms associated with mild cognitive impairment (MCI). Furthermore, we examined whether the relationship between MRI measures and clinical symptom onset was modified by apolipoprotein E (ApoE) genotype and level of cognitive reserve (CR). MRI scans and measures of CR were obtained at baseline from 245 participants who had been followed for up to 18 years (mean follow‐up 11 years). A composite score based on reading, vocabulary, and years of education was used as an index of CR. Cox regression models showed that lower baseline volume of the right hippocampus and smaller baseline thickness of the right entorhinal cortex predicted the time to symptom onset independently of CR and ApoE‐?4 genotype, which also predicted the onset of symptoms. The atrophy rates of bilateral entorhinal cortex and amygdala volumes were also associated with time to symptom onset, independent of CR, ApoE genotype, and baseline volume. Only one measure, the left entorhinal cortex baseline volume, interacted with CR, such that smaller volumes predicted symptom onset only in individuals with lower CR. These results suggest that MRI measures of medial temporal atrophy, ApoE‐?4 genotype, and the protective effects of higher CR all predict the time to onset of symptoms associated with MCI in a largely independent, additive manner during the preclinical phase of Alzheimer's disease. Hum Brain Mapp 36:2826–2841, 2015. © 2015 Wiley Periodicals, Inc.     

Intrinsic functional connectivity of the human medial temporal lobe suggests a distinction between adjacent MTL cortices and hippocampus

Functional connectivity analyses can offer insights into mechanisms of the brain that might not be revealed by traditional fMRI. These analyses compare seed voxels' activity over time to the activity of other voxels over time and identify correlations between regions. This study is the first to perform functional connectivity analyses in the human medial temporal lobe (MTL) at high enough resolution to resolve the hippocampal subfields. We calculated the average correlation coefficients between the MTL cortices, which include the entorhinal (ERC), perirhinal (PRC), and parahippocampal cortex (PHC), and the hippocampal subfields dentate gyrus/CA3, CA1, and subiculum. We found that the hippocampal subfields had relatively high correlations with each other both within and across hemispheres, but did not have exceptionally strong correlations with the MTL cortices. The opposite was also seen where there was a relatively high correlation coefficient between the ERC and PRC, but both regions had low correlation coefficients with the hippocampal subfields. We also found greater functional connectivity within a hemisphere than across hemispheres. These effects were replicated across multiple datasets which differed in task demands, participants' age, and scanner sequence/slice acquisition. Notably, all datasets were better correlated to these patterns of intrinsic functional connectivity than to a model based on anatomical constraints. This is consistent with evidence that functional connectivity is not a direct mapping of anatomical connectivity. These patterns of functional connectivity imply a distinction between the MTL cortices and the hippocampus and speak to our understanding of the organization of the MTL. © 2012 Wiley Periodicals, Inc.     

Volume determination of amygdala and hippocampus at 1.5 and 3.0T MRI in temporal lobe epilepsy

Since magnetic resonance imaging (MRI) technique is constantly evolving with higher field strength scanners, the question arises whether images from different field strength scanners can be used interchangeably for scientific and clinical purposes. We address this issue in a study group of patients with temporal lobe epilepsy (TLE). Two different quantification methods for analysing structural (MRI) were used. Conventional volumetry was performed by manually tracing amygdala and hippocampus volumes on both 1.5 and 3T scans of 10 TLE patients. Additionally a voxel-based morphometry (VBM)-based extraction of those structures was conducted. As an answer to the main question, it was determined that the volumetrically derived volumes of amygdala and hippocampus from 1.5 and 3.0T images did not differ. Our findings concerning the volumetry are consistent with findings in healthy controls, thus offering the possibility to use volumetry of the different scanners interchangeably. The results of the VBM-analyses show satisfying inter-scanner volume quantification but not consistent enough to be deemed interchangeable. Further investigations analysing the outcomes of conventional VBM of different field strength scanners are necessary.     

Efficacy of temporal lobe surgery for epilepsy in patients with negative MRI for mesial temporal lobe sclerosis

Epilepsy surgery is a successful treatment for refractory temporal lobe epilepsy (TLE). Reports suggest fewer seizure-free outcomes for patients with TLE and who have a negative brain MRI (nMRI) for mesial temporal sclerosis. Data were collected prospectively from patients with nMRI who underwent temporal lobe surgery for TLE characterized by unilateral ictal temporal lobe seizure onset based on a scalp video electroencephalogram or invasive subdural electrode recordings. A total of 86 patients were followed for at least 24 months after surgery. Outcome was evaluated using the Engel classification. Seizure control was obtained by 55% (47/86) of patients (Class [CL]-I), 27% (23/86) showed significant improvement (CL-II) and 19% (16/86) were deemed surgical failures. Shorter duration of epilepsy, later onset of seizures, and ictal theta rhythm (5-7 Hz) were the most significant predictors of postoperative seizure control. Although hypometabolism on positron emission tomography scan and significant memory disparity (>2.5/8) were not significant prognosticators independently, cumulatively they were predictors for favorable outcome.