Hippocampal response to visual objects is related to visual memory functioning

The medial temporal lobe participates not only in episodic memory, but also in visual object processing. Here we asked whether these processes are linked within the human hippocampus. To this end, we recorded field potentials directly from the hippocampus proper during a visual object decision task in temporal lobe epilepsy patients with either normal or below normal visual memory performance. Only in patients with normal visual memory, did the hippocampus proper differentiate reliably between real and nonsense objects, whereas neural responses to both kinds of objects were virtually the same in patients whose visual memory performance was reduced. These findings suggest that neural responses to visual objects within the hippocampus proper are directly linked to visual memory performance.     

Semantic memory in partial epilepsy: verbal and non-verbal deficits and neuroanatomical relationships

Semantic memory was evaluated in 124 epilepsy patients, including 84 with left (n=44) or right temporal lobe epilepsy (TLE) (n=40) and 40 with left (n=25) or right frontal lobe epilepsy (FLE) (n=15), in order to determine their verbal and visual deficits, and the neuroanatomical relationships between them. The controls were 35 healthy subjects. Semantic memory was assessed by means of Picture Naming, Picture Pointing, the verbal Pyramid and Palm Trees Test (PPTT), the visual PPTT, Object Decision Hard, and Drawing From Memory. Episodic memory was assessed by means of the Short Story, Rey's Complex Figure, the Verbal and Visual Selective Reminding Procedure and Brown-Peterson Procedure. Factor analysis of the epilepsy patients distinguished their semantic memory scores from other neuropsychological domains. The semantic memory factor was significantly related to the side of the epileptic region, with lower scores in the left hemisphere and left TLE patients. In comparison with the controls, the left TLE patients were significantly impaired on Picture Naming, Picture Pointing, and Object Decision Hard. Subsequent analyses showed that, in comparison with the controls and the right TLE patients, the left TLE patients with lateral temporal lobe lesions were impaired in Picture Naming whereas, in comparison with the controls, the left TLE patients with mesial temporal lobe lesions were impaired in Object Decision Hard. On the contrary, the episodic memory factor was not related to the side of the epileptic region, and a few material-specific tests revealed opposite impairments in the left and right hemisphere patients. These results show that left TLE may cause semantic memory deficits involving verbal and visual information. Unlike the material-specific pattern of episodic memory, this pattern of impairment is in line with the view of an amodal semantic store in which all of the information about a thing overlaps. The semantic memory impairment may reflect damage in the lateral and mesial temporal lobe regions that impair neocortical functions in storing and retrieving information or hippocampal functions in processing meaningful stimuli.     

颞叶癫痫的痫性放电传导和临床症状的颅内电极脑电图研究

目的 探讨颞叶癫痫患者痫性放电的传导部位、时间和相应的临床症状变化.方法 对2003年6月至2007年5月确诊为颞叶癫痫并行颅内电极埋置检查的48例患者的颅内电极脑电图和发作期症状进行回顾性分析,通过在双侧海马放置的针状电极和颢叶、额叶等放置的条状皮层电极,找出发作起源部位、早期传导部位、传导时间及发作起始症状和传导后症状.结果 共记录126次临床癫痫发作,105次记录到传导部位,其中同侧颢叶内传导22次,额叶39次,顶枕叶18次,对侧海马10次,16次全脑放电.44.8%传导时间小于2.5 s,55.2%传导时间超过2.5 s,且有17.1%超过5 s.101次发作中出现初始症状,其中82.2%为意识水平下降、自动症、恐惧等;99次记录到传导后新症状,其中出现颞叶外传导者82.2%出现抽动或强直表现.结论 颞叶癫痫放电传导部位主要是同侧的额叶与颞叶内部,但也可直接到对侧海马结构,临床症状与传导位置有关,传导速度多较慢.     

Magnetoencephalographic study of rhythmic mid-temporal discharges in non-epileptic and epileptic patients.

To evaluate the source location and clinical significance of rhythmic mid-temporal theta discharges (RMTD) by MEG in non-epileptic and epileptic patients, we conducted simultaneous MEG and EEG recordings with a whole-scalp 306-channel neuromagnetometer in three patients: one with right temporal lobe epilepsy (TLE), one with right frontal lobe epilepsy (FLE), and one with tension headache. We visually detected the RMTD activity and interictal spikes, and then localised their generators by MEG source modelling. We repeated MEG measurement 3 months after right anterior temporal lobectomy (ATL) in the TLE patient; 3 months after anticonvulsant medication in the FLE patient. In epileptic patients, RMTD activities were found during drowsiness over the left temporal channels of both MEG and EEG recordings, and their generators were localised to the left posterior inferior temporal region. In the patient with tension headache, RMTD was localised in the right inferior temporal area. When the epileptic patients became seizure free with disappearance of epileptic spikes, RMTD was still found over the left temporal channels. Besides, some bursts of RMTD appeared also in the right temporal channels in our TLE patient after ATL. Our results indicate that the source of RMTD activity is located in the fissural cortex of the posterior inferior temporal region. As a physiologic rhythm related to dampened vigilance, RMTD has no direct relation to epileptogenic activity.     

Correlation of temporal lobe glucose metabolism with the Wada memory test

PURPOSE: The goal of the present study was to examine the relationship of 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) and the Wada memory test in lateralizing memory dominance and epileptic focus. METHODS: FDG-PET and the Wada test were performed in 18 patients with temporal lobe epilepsy (TLE). The asymmetry indices of FDG-PET (PET-AI) were calculated in mesial, polar, anterolateral, midlateral, and posterolateral regions of the temporal lobe, and those of Wada memory test (Wada-AI) were obtained as well. RESULTS: The Wada-AI was significantly correlated with PET-AI in mesial (r = 0.67, p = 0.003), polar (r = 0.55, p = 0.019), anterolateral (r = 0.55, p = 0.019), and midlateral (r = 0.51, p = 0.031) regions of the temporal lobe. However, after a linear regression analysis, PET-AI of only the mesial temporal region was significantly correlated with Wada-AI (p = 0.008). Wada-AI could correctly lateralize the seizure focus in 90% of the left TLE and 75% of the right TLE patients. The PET-AI of the mesial temporal region showed the highest sensitivity of seizure lateralization (80% of left TLE and 87.5% of right TLE). PET-AI of other temporal regions had lower sensitivities (50-80% of left TLE, 20-75% of right TLE). One or two patients showed false seizure lateralization by PET-AI on each temporal region. CONCLUSIONS: Although FDG-PET hypometabolism is observed at both mesial and lateral regions of the temporal lobe in mesial TLE, mesial temporal region appeared to be a dominant and leading area for lateralizing Wada memory dominance and epileptic focus.     

Temporal lobe interictal epileptic discharges affect cerebral activity in "default mode" brain regions

A cerebral network comprising precuneus, medial frontal, and temporoparietal cortices is less active both during goal-directed behavior and states of reduced consciousness than during conscious rest. We tested the hypothesis that the interictal epileptic discharges affect activity in these brain regions in patients with temporal lobe epilepsy who have complex partial seizures. At the group level, using electroencephalography-correlated functional magnetic resonance imaging in 19 consecutive patients with focal epilepsy, we found common decreases of resting state activity in 9 patients with temporal lobe epilepsy (TLE) but not in 10 patients with extra-TLE. We infer that the functional consequences of TLE interictal epileptic discharges are different from those in extra-TLE and affect ongoing brain function. Activity increases were detected in the ipsilateral hippocampus in patients with TLE, and in subthalamic, bilateral superior temporal and medial frontal brain regions in patients with extra-TLE, possibly indicating effects of different interictal epileptic discharge propagation.     

Preserved memory in temporal lobe epilepsy patients after surgery for low-grade tumour. A pilot study

The objective was to carry out a pilot study exploring memory outcome in patients with temporal lobe epilepsy (TLE) and low-grade tumour. A prospective study using a competence-related memory assessment was carried out in the Laboratory of Neuropsychology, Epilepsy Center and Neurosurgical Department of the “C. Besta” National Neurological Institute in 24 TLE patients undergoing surgical resection for left (n=12) or right (n=12) low-grade tumours and 36 healthy subjects. Patients underwent mesial or lateral temporal lobe lesionectomy. Neuropsychological tests exploring verbal and visual short-term memory, learning, delayed recall and ability to control interference in memory were applied. Before and after surgery, significant verbal impairment was present in left TLE patients compared to controls and right TLE patients, and visual deficits were present in both groups compared to controls. After surgery, there was no significant decrease in mean verbal or visual memory scores related to the operated side. Some memory abilities subserved by the contralateral temporal lobe improved. Postoperative memory scores were related to preoperative scores, side of operation, age and education. In patients with TLE and low-grade tumour, temporal lobe surgery does not necessarily induce memory deficits. Improvement of memory abilities subserved by the unoperated temporal lobe may be expected.     

Downregulation of gephyrin in temporal lobe epilepsy neurons in humans and a rat model

Gephyrin, which is a postsynaptic scaffolding protein participated in clustering GABA(A) receptors at inhibitory synapses, has been reported to be involved in temporal lobe epilepsy (TLE) recently. Here, we investigate gephyrin protein expression in the temporal lobe epileptic foci in epileptic patients and experimental animals in order to explore the probable relationship between gephyrin expression and TLE. Using immunohistochemistry, immunofluorescence, and western blot analysis, gephyrin expression was examined in 30 human temporal neocortex samples from patients who underwent surgery to treat drug-refractory TLE and 10 histological normal temporal neocortex from the controls. Meanwhile, we investigated the gephyrin expression in the hippocampus and adjacent neocortex from experimental rats on 24 h, 48 h, 1 week, 2 weeks, 1 month, and 2 months postseizure and from control rats. Gephyrin protein was mainly expressed in the membrane and cytoplasm of neurons in temporal lobe epileptic foci in humans and experimental rats. Gephyrin expression was significantly lower in the temporal neocortex of TLE patients compared to the controls. In experimental rats, the expression of gephyrin in temporal lobe was downregulated in epileptic groups compared to the control group. Gephyrin expression gradually decreased during the acute period and the latent period, but then began to increase below the levels seen in controls during the chronic phase. Our findings suggest that gephyrin may be involved in the development of TLE.     

Memory impairment in humans after bilateral damage to lateral temporal neocortex

The hippocampus and its adjacent medial temporal regions are crucial for episodic memory. However, it is far less obvious whether other temporal regions beyond the medial part are important for memory processing. The memory performance of a group of patients with bilateral lesions over the lateral temporal lobe sparing the hippocampus was assessed and compared with that of patients with relatively spared cortex and patients with bilateral damage to the lateral temporal lobe and the hippocampus. The results demonstrate that bilateral damage to the lateral temporal lobe results in memory impairment across verbal and visual modalities.     

Can postictal memory predict postoperative memory in patients with temporal lobe epilepsy?

We investigated the contribution of postictal memory testing for lateralizing the epileptic focus and predicting memory outcome after surgery for temporal lobe epilepsy (TLE). Forty‐five patients with TLE underwent interictal, postictal, and postoperative assessment of verbal and nonverbal memory. Surgery consisted of anterior temporal lobectomy (36), selective isolated amygdalohippocampectomy (6), or amygdalohippocampectomy coupled to lesionectomy (3). Postictal and postoperative but not interictal memory were significantly lower in left TLE than in right TLE. Nonverbal memory showed no significant difference in left TLE versus right TLE in all conditions. Postictal memory was significantly correlated with postoperative memory, but the effect disappeared when the lateralization of the focus was considered. Postictal verbal memory is a useful bedside tool that can help lateralize the epileptic focus. Larger studies are needed to further estimate its predictive value of the postoperative outcome.     

Spatial navigation impairment in patients with refractory temporal lobe epilepsy: evidence from a new virtual reality-based task

This study was aimed at examining spatial learning and memory in nonoperated temporal lobe epilepsy (TLE). Twenty-five patients with a refractory epileptic focus located in the temporal lobe (10 in the right hemisphere and 15 in the left hemisphere) and 25 healthy age-matched controls performed the "Boxes Room," a virtual reality version of the holeboard. They were trained in 10 trials to locate the reward boxes in a room with 16 of them available. Participants also completed a comprehensive neuropsychological evaluation. Patients performed significantly worse relative to the control group. They traveled longer distances and committed more errors than controls. No differences in performance were found within the TLE group when gender or lateralization of the epileptic focus was considered an independent variable. These findings suggest that the integrity of temporal structures in both hemispheres could be critical to spatial learning and memory and support the spatial component of the task.     

颞叶癫 的EEG和MR术前定位研究

目的：探讨 ＥＥＧ、ＭＲ对颞叶癫癎（ＴＬＥ）术前定位。方法：用 ＭＲ、ＥＥＧ对 ２０例 ＴＬＥ病例进行术前定位,与术中 ＥＥＧ和术后随访结果比较。结果：２０例病例中１７例依据ＭＲ及ＥＥＧ获得定位,主要在海马区域病变１２例,前颞叶５例．另３例ＭＲ检查正常,依据多次ＥＥＧ检查获得定位,随访疗效满意。结论：ＥＥＧ是诊断ＴＬＥ的重要手段,ＭＲ可对继发性ＴＬＥ作出正确诊断,ＭＲ对海马硬化检查可协助ＥＥＧ对ＴＬＥ定位诊断。     

Effects of illness duration on memory processing of patients with temporal lobe epilepsy

PURPOSE: To examine the effects of illness duration on the neural processing of memory in patients with temporal lobe epilepsy (TLE) by using functional MRI. METHODS: Twenty-three TLE patients (16 left, seven right) performed a complex visual scene-encoding task during functional MRI. Region-of-interest (ROI) analyses were used to quantity functional activation in the mesial temporal and frontal lobes. The patients' verbal and visual memory performances were evaluated by standardized neuropsychological tests. Analyses included group comparison and correlations of duration of epilepsy with functional activation and memory performance. RESULTS: Compared with normal controls, TLE patients demonstrated reduced activation bilaterally in the mesial temporal lobe (p=0.003), and the reduction was more pronounced on the ipsilateral side of the seizure focus. Moreover, a longer duration of illness was associated with fewer voxels activated in both the left (p=0.038) and right (p=0.017) mesial temporal lobe. Furthermore, the duration of illness was found to be significantly and negatively correlated with both verbal (p=0.020) and visual (p=0.000) memory functioning. CONCLUSIONS: TLE seems to affect the memory processes in the mesial temporal lobes progressively (i.e., the longer the duration of illness, the lower the brain activation). In turn, the reduction of brain activation negatively affects memory functioning. Finally, the reduction is not limited to the side of seizure but also is observed in the contralateral hemisphere.     

A controlled quantitative MRI volumetric investigation of hippocampal contributions to immediate and delayed memory performance

MRI volumetric TLE studies show inconsistent evidence of hippocampal involvement in memory. Prior studies have not dissociated hippocampal and temporal lobe contributions to memory. We measured hippocampal and temporal lobe volumes and immediate/delayed memory performances in 64 TLE patients. Regression was used to dissociate hippocampal from temporal lobe contributions to memory. Results revealed reliable evidence for dominant hippocampal involvement in delayed verbal recall across three separate measures and less consistent evidence for nondominant hippocampal involvement. The findings point to a consistent relationship of dominant hippocampal volumes to delayed verbal recall but no involvement of the temporal lobe or nondominant hippocampus in memory.     

Visual presentation of novel objects and new spatial arrangements of objects differentially activates the medial temporal lobe subareas in humans

A number of studies in rodents and monkeys report a distinction between the contributions of the hippocampus and perirhinal cortex to memory, such that the hippocampus is crucial for spatial memory whereas the perirhinal cortex has a pivotal role in perception and memory for visual objects. To determine if there is such a distinction in humans, we conducted a functional magnetic resonance imaging study to compare the medial temporal lobe responses to changes in object identity and spatial configurations of objects. We found evidence for the predicted distinction between hippocampal and perirhinal cortical activations, although part of the hippocampus was also activated by identification of novel objects. Additionally, an anterior-posterior activation gradient emerged inside the hippocampus and parahippocampal cortex. The anterior hippocampus, perirhinal cortex and anterior parahippocampal cortex are involved in perception of contextually novel objects, whereas the posterior hippocampus and posterior parahippocampal cortex are involved in processing of novel arrangements of familiar objects. These results demonstrate that there is a functional dissociation between processing of novel object identities and new spatial locations of objects among the subregions of medial temporal lobe structures in humans also.     

When should a resection sparing mesial structures be considered for temporal lobe epilepsy?

Anteromesial temporal lobectomy (AMTL) is an effective and safe treatment for refractory temporal lobe epilepsy (TLE) caused by hippocampal sclerosis (HS). It is possible that modifications to this procedure could offer improved seizure control or a reduction in functional consequences in some patients. Reviewed here is the issue of when it might be appropriate to perform a resection for TLE that spares the mesial structures, particularly the hippocampus and parahippocampal gyrus. This issue is particularly important for dominant hemipshere TLE and for patients without obvious HS, as these are the patients at greatest risk for verbal memory decline following AMTL. Current evidence suggests that mesial structure-sparing resections may be worth consideration for two types of patients: those with temporal lobe foreign tissue lesions outside the mesial structures, and those with temporal lobe hypometabolism on fluorodeoxyglucose positron emission tomography but a normal MRI. Patients with dual pathology (i.e., HS plus another epileptogenic lesion) are unlikely to benefit from a resection that spares the mesial temporal lobe. There is little evidence to state whether resections of this kind are worthwhile for cryptogenic TLE, or for mesial TLE with preserved memory function. There is a clear need to move beyond the field's present focus on the hippocampus and investigate new approaches to TLE that may minimize the risks of functional consequences in patients without HS.     

Neural correlates of verbal semantic memory in patients with temporal lobe epilepsy

Functional imaging data suggest that the core network engaged in verbal semantic memory (SM) processing encompasses frontal and temporal lobe structures, with a strong left lateralization in normal right handers. The impact of long term temporal lobe epilepsy (TLE) on this network has only partly been elucidated. We studied verbal SM in 50 patients with chronic, intractable TLE (left TLE=26, right TLE=24) and 35 right handed normal controls using a verbal fMRI semantic decision paradigm. All patients had language lateralized to the left hemisphere, as verified by the intracarotid amobarbital procedure. Within and between group analyses showed remarkable, group-specific activation profiles. The control group activated frontal and temporal areas bilaterally, with a strong left predominance. Left TLE patients showed a shift of activations of left frontal and medial temporal areas to homologous regions in the right hemisphere. Furthermore, left TLE subjects utilized subcortical structures such as the thalamus and putamen to accomplish the verbal SM task. Contrastively, the activation pattern of right TLE patients resembled that of normal controls, but exhibited "hypofrontality" with a shift from frontal to posterior regions in the temporal, parietal and occipital lobe. Our results show that chronic epileptic activity originating from temporal seizure foci is associated with an alteration of neural circuits which support semantic language processing and that side of seizure focus has a specific impact on the resulting activation network. These findings presumably result from morphological changes and from functional reorganization which are both inherent to chronic TLE.     

Decreased basal fMRI functional connectivity in epileptogenic networks and contralateral compensatory mechanisms

A better understanding of interstructure relationship sustaining drug-resistant epileptogenic networks is crucial for surgical perspective and to better understand the consequences of epileptic processes on cognitive functions. We used resting-state fMRI to study basal functional connectivity within temporal lobes in medial temporal lobe epilepsy (MTLE) during interictal period. Two hundred consecutive single-shot GE-EPI acquisitions were acquired in 37 right-handed subjects (26 controls, eight patients presenting with left and three patients with right MTLE). For each hemisphere, normalized correlation coefficients were computed between pairs of time-course signals extracted from five regions involved in MTLE epileptogenic networks (Brodmann area 38, amygdala, entorhinal cortex (EC), anterior hippocampus (AntHip), and posterior hippocampus (PostHip)). In controls, an asymmetry was present with a global higher connectivity in the left temporal lobe. Relative to controls, the left MTLE group showed disruption of the left EC-AntHip link, and a trend of decreased connectivity of the left AntHip-PostHip link. In contrast, a trend of increased connectivity of the right AntHip-PostHip link was observed and was positively correlated to memory performance. At the individual level, seven out of the eight left MTLE patients showed decreased or disrupted functional connectivity. In this group, four patients with left TLE showed increased basal functional connectivity restricted to the right temporal lobe spared by seizures onset. A reverse pattern was observed at the individual level for patients with right TLE. This is the first demonstration of decreased basal functional connectivity within epileptogenic networks with concomitant contralateral increased connectivity possibly reflecting compensatory mechanisms.     

导航引导下保留侧脑室完整的颞叶癫痫手术26例体会

目的探讨神经导航下保留侧脑室完整的前颞叶海马、杏仁核切除术治疗颞叶癫痫的效果。方法将26例神经导航下保留侧脑室完整的前颞叶海马切除术后患者的术前Wada试验评估、术后并发症及癫痫控制情况进行分析。结果术后随访时间24～36月,EngelⅠ级22例（85％）,EngelⅡ级3例（11％）,EngelⅢ例（4％）。术后1例（4％）患者出现记忆减退症状,4例患者发生视野缺损。结论同时切除海马、杏仁核的标准前颞叶切除术为外科治疗颞叶癫痫的有效术式,术前Wada试验评估能很好的预测手术对患者记忆功能的影响,保留侧脑室完整的术式可减少视野缺损的发生。     

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.