Associative encoding of pictures activates the medial temporal lobes

It remains unresolved whether the medial temporal lobe activations found in recent neuroimaging studies are mediated by novelty detection alone, by specific kinds of encoding or consolidation operations, or both. This study attempted to see whether associative encoding or consolidation is sufficient to cause such activation by matching for novelty across conditions. Using single-photon emission computer tomography (SPECT) (with Tc^99mHMPAO), we compared the activation patterns produced by the associative encoding and the perceptual matching of novel complex scenes in 10 normal subjects using both statistical parametric mapping (SPM) and a regions-of-interest (ROI) approach. During the encoding condition, significant activations were detected in the left hippocampal/parahippocampal region, the left cingulate cortex, and the right prefrontal cortex, using both statistical techniques. Additionally, activation was found in the right cingulate cortex, and a trend towards activation was found in the right hippocampal/parahippocampal region using the ROI approach. In contrast, no medial temporal activations were found during the matching condition, which produced bilateral occipito-parietal and right posterior inferior parietal (supramarginal gyrus) activations. These results not only confirm that the associative encoding and/or consolidation of complex scenes is partially mediated by medial temporal lobe structures, but also demonstrate, for the first time, that associative encoding/consolidation is sufficient to produce such an activation. The implications of the high degree of consistency revealed by the results of the SPM and ROI comparison are discussed. Hum. Brain Mapping 6:85–104, 1998. © 1998 Wiley-Liss, Inc.     

Conceptual and perceptual novelty effects in human medial temporal cortex

Medial temporal lobe (MTL) structures often respond to stimulus repetition with a reduction in neural activity. Such novelty/familiarity responses reflect the mnemonic consequences of initial stimulus encounter, although the aspects of initial processing that lead to novelty/familiarity responses remain unspecified. The current functional magnetic resonance imaging (fMRI) experiment examined the sensitivity of MTL to changes in the semantic representations/processes engaged across stimulus repetitions. During initial study blocks, words were visually presented, and participants made size, shape, or composition judgments about the named referents. During repeated study blocks, the initial words were visually re-presented along with novel words, and participants made size judgments for all items. Behaviorally, responses were faster to repeated words in which the same task was performed at initial and repeated exposure (i.e., size-->size) relative to repeated words in which the tasks differed (i.e., composition-->size and shape-->size). fMRI measures revealed activation reductions in left parahippocampal cortex following same-task and different-task repetition; numerically, the effect was larger in the same-task condition. Accordingly, left parahippocampal cortex demonstrates sensitivity to perceptual novelty/familiarity, and it remains unclear whether this region also is sensitive to novelty/familiarity in the conceptual domain. In left perirhinal cortex, a novelty/familiarity effect was observed in the same-task condition but not in the different-task condition, thus revealing sensitivity to the degree of semantic overlap across exposures but insensitivity to perceptual repetition of the visual word form. Perirhinal sensitivity to semantic repetition and insensitivity to perceptual repetition suggests that human perirhinal cortex receives conceptual inputs, with perirhinal contributions to declarative memory perhaps partially stemming from its role in processing semantic aspects of experiences.     

海马有病损的颞叶内侧癫(癎)手术15例临床分析

目的 探讨海马有病损的颞叶内侧癫(癎)的手术价值.方法 回顾性分析经手术治疗的15例伴有海马病损颞叶内侧癫(癎)患者.均经详细了解发作症状学、附加蝶骨电极的长程视频脑电图及颅脑磁共振等检查;经正规而详尽的术前评估,行前颞叶切除术,术后随访至少半年以上.结果 术后依据Engel分级,显效(Ⅰ级和Ⅱ级)占80.0％ (12/15)、好转(Ⅲ级)占20.0％(3/15)、无效(Ⅳ级)为0.0％.结论 颞叶内侧癫(癎)手术效果确切,是基层医院开展癫(癎)手术的理想选择.     

Fine-tuned coupling between human parahippocampal ripples and sleep spindles

Sleep-associated memory consolidation is thought to rely on coordinated information transfer between the hippocampus and neocortex brought about during slow wave sleep (SWS) by distinct local field potential oscillations. Specifically, findings in animals have led to the concept that ripples originating from hippocampus combine with spindles to provide a fine-tuned temporal frame for a persistent transfer of memory-related information to the neocortex. The present study focused on characterizing the temporal relationship between parahippocampal ripple activity (80-140 Hz) and spindles recorded from frontal, parietal and parahippocampal cortices in 12 epilepsy patients implanted with parahippocampal foramen ovale electrodes. Overall, parietal and parahippocampal spindles showed closer relationships to parahippocampal ripple activity than frontal spindles, with the latter following parietal and parahippocampal spindles at a variable delay of up to 0.5 s. On a timescale of seconds, ripple activity showed a continuous increase before the peak of parietal and parahippocampal spindles, and decreased thereafter. At a fine timescale of milliseconds, parahippocampal ripple activity was tightly phase-locked to the troughs of these spindles. The demonstration of spindle phase-locked ripple activity in humans is consistent with the idea of a temporally fine-tuned hippocampus-to-neocortex transfer of information taking place during SWS.     

Rhinal-hippocampal EEG coherence is reduced during human sleep

The deficiency of declarative memory compared with waking state is an often overlooked characteristic of sleep. Here, we investigated whether rhinal-hippocampal coherence, an electrophysiological correlate of declarative memory formation, is significantly altered during sleep as compared with waking state. For this purpose, we analysed recordings of intracranial EEG activity during sleep obtained directly from within the medial temporal lobe in patients with unilateral temporal lobe epilepsy. We found a general reduction of rhinal-hippocampal EEG coherence during sleep compared with waking state, which was most pronounced within the upper gamma bands (average decrease up to 56%). The observed coherence changes clearly differ from findings reported for surface EEG data and thus appear to be specific for the medial temporal lobe. The decrease of rhinal-hippocampal EEG coherence from waking state towards sleep may yield an electrophysiological explanation for the sleep-related deficiency of declarative memory.     

头部MRI阴性的颞叶内侧癫痫患者认知功能障碍研究

目的评估头部MRI阴性颞叶内侧癫痫(MTLE)患者认知功能受损特点。方法回顾性分析27名头部MRI阴性的MTLE患者资料,其中左侧MTLE 14例(左侧MTLE组),右侧MTLE 13例(右侧MTLE组)。癫痫患者与性别、年龄和受教育程度严格匹配的14名健康对照者(对照组)均接受蒙特利尔认知评估量表(Mo CA)和失礼识别任务的测评。结果在Mo CA得分方面,两组MTLE患者的Mo CA总分及各分项测试得分均低于对照组(P 0. 05);右侧MTLE组复制立方体得分低于左侧MTLE组和对照组(P 0. 05);右侧MTLE组的画钟试验得分低于左侧MTLE组(P 0. 05);左侧MTLE组句子复述、语言流畅性测试得分低于右侧MTLE组(P 0. 05)。在失礼识别任务得分方面,两组MTLE患者得分均低于对照组(P 0. 05);左侧MTLE组比右侧MTLE组更低(P 0. 05)。结论头部MRI阴性MTLE患者的一般认知功能及高级社会认知功能均受损。     

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.     

Differential contributions of the anterior temporal and medial temporal lobe to the retrieval of memory for person identity information

Although previous studies have suggested the importance of the bilateral anterior temporal (ATL) and medial temporal lobes (MTL) in the retrieval of person identity information, there is little evidence concerning how these regions differentially contribute to the process. Here we investigated this question using functional magnetic resonance imaging (fMRI). Before scanning, subjects learned associations among faces (F), names (N), and job titles (as a form of person-related semantics, S). During retrieval with fMRI, subjects were presented with previously learned and new S stimuli, and judged whether the stimuli were old or new. Successful retrieval (H) trials were divided into three conditions: retrieval of S and associated F and N (HSFN); retrieval of S and associated F (HSF); and retrieval of S only (HS). The left ATL was significantly activated in HSFN, compared to HSF or HS, whereas the right ATL and MTL were significantly activated in HSFN and HSF relative to HS. In addition, activity in bilateral ATL was significantly correlated with reaction time for HSFN, whereas we found no significant correlation between activity in the right MTL and reaction time in any condition. The present findings suggest that the left ATL may mediate associations between names and person-related semantic information, whereas the right ATL mediates the association between faces and person-related semantic information in memory for person identity information. In addition, activation of the right MTL region implies that this area may contribute to a more general relational processing of associative components, including memory for person identity information.     

Memory loss due to transient hypoperfusion in the medial temporal lobes including hippocampus

A typical case of transient global amnesia (TGA) was investigated with single photon emission computed tomography (SPECT) and magnetic resonance imaging (MRI) with 1.5-tesler scans. During the amnesic episode, a marked decrease of cerebral blood flow was observed in the areas confined to the territory of the bilateral posterior cerebral arteries including the hippocampus. After the episode, cerebral blood flow returned to normal and a circumscribed lesion was detected in the middle portion of CA 1 field of the left hippocampus. The SPECT findings prove direct evidence that the medial temporal structures are involved in the establishment of new memories, as well as in process of recalling only recently acquired memories, but not in retrieval of memories acquired long ago. The MRI findings indicate that a unilateral partial damage to CA 1 sector of the hippocampus does not develop a definite memory impairment and that high-resolution MRI study on the hippocampus is necessary in TGA patients.     

Cortical oscillations in human medial temporal lobe during wakefulness and all-night sleep

We have recorded human medial temporal lobe electrocorticogram during wakefulness and natural sleep in epileptic patients with subdural electrodes. From these recordings, we have found gamma (30-150 Hz) [Neuroscience 90 (1999) 1149] and beta-1 (10-20 Hz) [NeuroReport 10 (1999) 3055] activities during wakefulness in human medial temporal lobe. In this paper, we will report changes of these frequencies across wake and natural sleep. Electrocorticograms during wake, slow wave sleep and rapid eye movement (REM) sleep were subjected to fast Fourier transformation analysis. During wake two spectral enhancements, beta-1 and gamma, were consistently observed across subjects. In the raw signal, beta-1 was observed as a regular rhythmic oscillation. In slow wave sleep, the beta-1 peak disappeared but gamma remained, although slightly reduced in power. During REM sleep, beta-1 appeared again, but the peak frequency was significantly lower than during wake (mean frequency: wake=16.6, REM=12.8 Hz). The gamma peak was also present in REM sleep. It has been known that the rhythmic slow activity (RSA) or theta is observed in some animals. However, it is unclear whether the human hippocampus displays similar activity. Since human beta-1 appears during wake and REM sleep when RSA is observed in other species, and since beta-1 is also a regular rhythmic oscillation, we propose that beta-1 may be the functional equivalent of hippocampal RSA (theta) observed in some animals. Functional significances of the gamma activity should be further investigated.     

Estimation of generator sources of human sleep spindles by dipole tracing method

Equivalent dipole sources of two types of human sleep spindles (14 and 12 Hz) were investigated on five normal subjects. The present study showed that a sleep spindle can be represented by a single equivalent dipole. For both 14 and 12 Hz sleep spindles, the equivalent dipole sources were estimated near the thalamus. The orientation of the equivalent dipole of a 14 Hz sleep spindle was in the centro-parietal direction, while that of a 12 Hz sleep spindle was in the frontal direction. These results suggest that both types of sleep spindle activities are generated in the thalamus, and cortical de-arousal plays a modificatory role on their different topographical distributions.     

内侧颞叶在P300产生中的作用--左颞叶切除术后1例患者的事件相关电位研究

目的探讨内侧颞叶(MTL)在P300产生中的作用。方法对1例左颞叶切除的患者和17名健康对照者进行视、听两种模式下的P300研究。结果患者的视、听P300潜伏期(PL)、波幅(Amp)和侧性分布均在对照组确定的正常范围之内。结论一侧MTL结构切除并不影响事件相关电位的内源性成分P300，P300的产生可能是脑多个部位共同活动的电位综合。     

High-resolution fMRI investigation of the medial temporal lobe

The medial temporal lobe (MTL) is critical for declarative memory formation. Several theories of MTL function propose functional distinctions between the different structures of the MTL, namely the hippocampus and the surrounding cortical areas. Furthermore, computational models and electrophysiological studies in animals suggest distinctions between the subregions of the hippocampus itself. Standard fMRI resolution is not sufficiently fine to resolve activity on the scale of hippocampal subregions. Several approaches to scanning the MTL at high resolutions have been made, however there are limitations to these approaches, namely difficulty in conducting group-level analyses. We demonstrate here techniques for scanning the MTL at high resolution and analyzing the high-resolution fMRI data at the group level. To address the issue of cross-participant alignment, we employ the ROI-LDDMM alignment technique, which is demonstrated to result in smaller alignment errors when compared with several other common normalization techniques. Finally, we demonstrate that the pattern of activation obtained in the high-resolution functional data is similar to that obtained at lower resolution, although the spatial extent is smaller and the percent signal change is greater. This difference in the pattern of activation may be due to less partial volume sampling in the high-resolution data, resulting in more accentuated regions of activation.     

Identification of the human medial temporal lobe regions on magnetic resonance images

The medial temporal lobe (MTL) plays a key role in learning, memory, spatial navigation, emotion, and social behavior. The improvement of noninvasive neuroimaging techniques, especially magnetic resonance imaging, has increased the knowledge about this region and its involvement in cognitive functions and behavior in healthy subjects and in patients with various neuropsychiatric and neurodegenerative disorders. However, cytoarchitectonic boundaries are not visible on magnetic resonance images (MRI), which makes it difficult to identify precisely the different parts of the MTL (hippocampus, amygdala, temporopolar, perirhinal, entorhinal, and posterior parahippocampal cortices) with imaging techniques, and thus to determine their involvement in normal and pathological functions. Our aim in this study was to define neuroanatomical landmarks visible on MRI, which can facilitate the examination of this region. We examined the boundaries of the MTL regions in 50 post‐mortem brains. In eight cases, we also obtained post‐mortem MRI on which the MTL boundaries were compared with histological examination before applying them to 26 in vivo MRI of healthy adults. We then defined the most relevant neuroanatomical landmarks that set the rostro‐caudal limits of the MTL structures, and we describe a protocol to identify each of these structures on coronal T1‐weighted MRI. This will help the structural and functional imaging investigations of the MTL in various neuropsychiatric and neurodegenerative disorders affecting this region. Hum Brain Mapp 35:248–256, 2014. © 2012 Wiley Periodicals, Inc.     

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.     

Different maturational changes of fast and slow sleep spindles in the first four years of life

Objective/BackgroundMassive changes in brain morphology and function in the first years of life reveal a postero-anterior trajectory of cortical maturation accompanied by regional modifications of NREM sleep. One of the most sensible marker of this maturation process is represented by electroencephalographic (EEG) activity within the frequency range of sleep spindles. However, direct evidence that these changes actually reflect maturational modifications of fast and slow spindles still lacks.Our study aimed at answering the following questions:1. Do cortical changes at 11.50 Hz frequency correspond to slow spindles?2. Do fast and slow spindles show different age trajectories and different topographical distributions?3. Do changes in peak frequency explain age changes of slow and fast spindles?Patients/MethodsWe measured the antero-posterior changes of slow and fast spindles in the first 60 min of nightly sleep of 39 infants and children (0–48 mo.).ResultsWe found that (A) changes of slow spindles from birth to childhood mostly affect frontal areas (B) variations of fast and slow spindles across age groups go in opposite direction, the latter progressively increasing across ages; (C) this process is not merely reducible to changes of spindle frequency.ConclusionsAs a main finding, our cross-sectional study shows that the first form of mature spindle (i.e., corresponding to the adult phasic event of NREM sleep) is marked by the emergence of slow spindles on anterior regions around the age of 12 months.     

Extrahippocampal gray matter atrophy and memory impairment in patients with medial temporal lobe epilepsy

Memory impairment observed in patients with medial temporal lobe epilepsy (MTLE) is classically attributed to hippocampal atrophy. The contribution of extrahippocampal structures in shaping memory impairment in patients with MTLE is not yet completely understood, even though atrophy in MTLE extends beyond the hippocampus. We aimed to evaluate the neuropsychological profile of patients with MTLE focusing on memory, and to investigate whether gray matter concentration (GMC) distribution within and outside the medial portion of the temporal lobes would be associated with their neuropsychological performance. We performed a voxel based morphometry study of 36 consecutive patients with MTLE and unilateral hippocampal atrophy. We observed a significant simple regression between general and verbal memory performance based on Wechsler Memory Scale-Revised and the GMC of medial temporal and extratemporal structures in patients with left MTLE. We also performed a "regions of interest analysis" of the medial temporal lobe, and we observed that the GMC of the hippocampus, entorhinal, and perirhinal cortices were consistently associated with general and verbal memory performance in patients with MTLE. We also observed that the GMC of the cingulate and orbito-frontal cortex are independently associated with verbal and general memory performances. Our results suggest that general and verbal memory impairments in patients with left MTLE are associated with atrophy of the hippocampus, the entorhinal, and the perirhinal cortex. We also suggest that atrophy and dysfunction of limbic and frontal structures such as the cingulate and the orbito-frontal cortex contribute to memory impairment in MTLE.     

Absence of an early hippocampal encoding signal after medial temporal lesions: No consequence for the spacing effect

Immediately repeated meaningful pictures in a continuous recognition task induce a positive frontal potential at about 200–300 ms, which appears to emanate from the medial temporal lobe (MTL) centered on the hippocampus, as concluded from inverse solutions, coherence measurements, and depth electrode recordings in humans. In this study, we tested patients with unilateral MTL lesions due to stroke to verify the provenance of this signal and its association with the spacing effect (SE)—the improved learning of material encountered in spaced rather than massed presentation. We found that unilateral left or right MTL lesions abolished the early frontal MTL‐mediated signal but not the spacing effect. We conclude that the SE does not depend on MTL integrity. We suggest that the early frontal signal at 200–300 ms after immediate picture repetition may serve as a direct biomarker of MTL integrity that may be useful in the early stages of diseases like Alzheimer's.     

立体定向热凝毁损海马杏仁核治疗海马病变所致难治性颞叶内侧癫

目的探讨立体定向手术热凝毁损海马杏仁核治疗海马病变所致难治性颞叶内侧癫癎的疗效。方法回顾分析19例由海马病变所致难治性颞叶内侧癫癎患者的临床表现、影像学（CT/MRI）脑电图（EEG/VEEG）资料和手术疗效。所有病例术前均行动态脑电图检查明确致癎灶完成定位诊断、术中行立体定向组织活检、快速冰冻病理确诊病变性质完成定性诊断。全部患者在计算机辅助下行致癎灶侧海马杏仁核立体定向热凝毁损术。手术效果按谭启富的评定标准进行评价。结果随访12～42个月，13例癫癎未再发作（满意），4例发作次数减少75%以上（明显改善），2例发作次数减少50%（改善）。未发现神经心理学改变及神经功能障碍等并发症。结论对于由海马病变所致难治性颞叶内侧癫癎，采用立体定向手术行海马杏仁核热凝毁损是控制癫癎发作的一种安全有效方法。     

Characterization of brain network supporting episodic memory in the absence of one medial temporal lobe

How the brain supports normal episodic memory function without medial temporal lobe (MTL) structures has not been well characterized, which could provide clues for new therapeutic targets for people with MTL dysfunction‐related memory impairment. To characterize brain network supporting effective episodic memory function in the absence of unilateral MTL, we investigated the whole‐brain cortical interactions during functional magnetic resonance imaging memory encoding paradigms of words and figures in patients who showed a normal range of memory capacity following unilateral MTL resection and healthy controls (HC). Compared to the HC, the patients showed less activation in the left inferior frontal areas and right thalamus together with greater activation in the many cortical areas including the medial prefrontal cortex (mPFC). Task‐based functional connectivity (FC) analysis revealed that the mPFC showed stronger interactions with widespread brain areas in both patient groups, including the hippocampus contralateral to the resection. Moreover, the strength of the mPFC FC predicts the individual memory capacity of the patients. Our data suggest that hyperconnectivity of distributed brain areas, especially the mPFC, is a neural mechanism for memory function in the absence of one MTL.