Resting‐state functional connectivity predicts the strength of hemispheric lateralization for language processing in temporal lobe epilepsy and normals

In temporal lobe epilepsy (TLE), determining the hemispheric specialization for language before surgery is critical to preserving a patient's cognitive abilities post‐surgery. To date, the major techniques utilized are limited by the capacity of patients to efficiently realize the task. We determined whether resting‐state functional connectivity (rsFC) is a reliable predictor of language hemispheric dominance in right and left TLE patients, relative to controls. We chose three subregions of the inferior frontal cortex (pars orbitalis, pars triangularis, and pars opercularis) as the seed regions. All participants performed both a verb generation task and a resting‐state fMRI procedure. Based on the language task, we computed a laterality index (LI) for the resulting network. This revealed that 96% of the participants were left‐hemisphere dominant, although there remained a large degree of variability in the strength of left lateralization. We tested whether LI correlated with rsFC values emerging from each seed. We revealed a set of regions that was specific to each group. Unique correlations involving the epileptic mesial temporal lobe were revealed for the right and left TLE patients, but not for the controls. Importantly, for both TLE groups, the rsFC emerging from a contralateral seed was the most predictive of LI. Overall, our data depict the broad patterns of rsFC that support strong versus weak left hemisphere language laterality. This project provides the first evidence that rsFC data may potentially be used on its own to verify the strength of hemispheric dominance for language in impaired or pathologic populations. Hum Brain Mapp, 36:288–303, 2015. © 2014 Wiley Periodicals, Inc.     

Patterns of altered functional connectivity in mesial temporal lobe epilepsy

Purpose: In mesial temporal lobe epilepsy (MTLE) the epileptogenic area is confined to the mesial temporal lobe, but other cortical and subcortical areas are also affected and cognitive and psychiatric impairments are usually documented. Functional connectivity methods are based on the correlation of the blood oxygen level dependent (BOLD) signal between brain regions, which exhibit consistent and reproducible functional networks from resting state data. The aim of this study is to compare functional connectivity of patients with MTLE during the interictal period with healthy subjects. We hypothesize that patients show reduced functional connectivity compared to controls, the interest being to determine which regions show this reduction. Methods: We selected electroencephalography–functional magnetic resonance imaging (EEG‐fMRI) resting state data without EEG spikes from 16 patients with right and 7 patients with left MTLE. EEG‐fMRI resting state data of 23 healthy subjects matched for age, sex, and manual preference were selected as controls. Four volumes of interest in the left and right amygdalae and hippocampi (LA, RA, LH, and RH) were manually segmented in the anatomic MRI of each subject. The averaged BOLD time course within each volume of interest was used to detect brain regions with BOLD signal correlated with it. Group differences between patients and controls were estimated. Key Findings: In patients with right MTLE, group difference functional connectivity maps (RMTLE ? controls) showed for RA and RH decreased connectivity with the brain areas of the default mode network (DMN), the ventromesial limbic prefrontal regions, and contralateral mesial temporal structures; and for LA and LH, decreased connectivity with DMN and contralateral hippocampus. Additional decreased connectivity was found between LA and pons and between LH and ventromesial limbic prefrontal structures. In patients with left MTLE, functional connectivity maps (LMTLE ? controls) showed for LA and LH decreased connectivity with DMN, contralateral hippocampus, and bilateral ventromesial limbic prefrontal regions; no change in connectivity was detected for RA; and for RH, there was decreased connectivity with DMN, bilateral ventromesial limbic prefrontal regions, and contralateral amygdala and hippocampus. Significance: In unilateral MTLE, amygdala and hippocampus on the affected and to a lesser extent on the healthy side are less connected, and are also less connected with the dopaminergic mesolimbic and the DMNs. Changes in functional connectivity between mesial temporal lobe structures and these structures may explain cognitive and psychiatric impairments often found in patients with MTLE.     

Extratemporal functional connectivity impairments at rest are related to memory performance in mesial temporal epilepsy

Mesial temporal lobe epilepsy (MTLE) is the most frequent form of focal epilepsy. At rest, there is evidence that brain abnormalities in MTLE are not limited to the epileptogenic region, but extend throughout the whole brain. It is also well established that MTLE patients suffer from episodic memory deficits. Thus, we investigated the relation between the functional connectivity seen at rest in fMRI and episodic memory impairments in MTLE. We focused on resting state BOLD activity and evaluated whether functional connectivity (FC) differences emerge from MTL seeds in left and right MTLE groups, compared with healthy controls. Results revealed significant FC reductions in both patient groups, localized in angular gyri, thalami, posterior cingulum and medial frontal cortex. We found that the FC between the left non‐pathologic MTL and the medial frontal cortex was positively correlated with the delayed recall score of a non‐verbal memory test in right MTLE patients, suggesting potential adaptive changes to preserve this memory function. In contrast, we observed a negative correlation between a verbal memory test and the FC between the left pathologic MTL and posterior cingulum in left MTLE patients, suggesting potential functional maladaptative changes in the pathologic hemisphere. Overall, the present study provides some indication that left MTLE may be more impairing than right MTLE patients to normative functional connectivity. Our data also indicates that the pattern of extra‐temporal FC may vary as a function of episodic memory material and each hemisphere's capacity for cognitive reorganization. Hum Brain Mapp 34:2202–2216, 2013. © 2012 Wiley Periodicals, Inc.     

Functional and structural changes in the memory network associated with left temporal lobe epilepsy

Understanding functional plasticity in memory networks associated with temporal lobe epilepsy (TLE) is central to predicting memory decline following surgery. However, the extent of functional reorganization within memory networks remains unclear. In this preliminary study, we used novel analysis methods assessing network‐level changes across the brain during memory task performance in patients with TLE to test the hypothesis that hippocampal functions may not readily shift between hemispheres, but instead may show altered intra‐hemispheric organization with unilateral damage. In addition, we wished to relate functional differences to structural changes along specific fibre pathways associated with memory function. Nine pre‐operative patients with intractable left TLE and 10 healthy controls underwent functional MRI during complex scene encoding. Diffusion tensor imaging was additionally performed in the same patients. In our study, we found no evidence of inter‐hemispheric shifts in memory‐related activity in TLE using standard general linear model analysis. However, tensor independent component analysis revealed significant reductions in functional connectivity between bilateral MTL, occipital and left orbitofrontal regions among others in left TLE. This altered orbitofrontal activity was directly related to measures of fornix tract coherence in patients (P < 0.05). Our results suggest that specific fibre pathways, potentially affected by MTL neurodegeneration, may play a central role in functional plasticity in TLE and highlight the importance of network‐based analysis approaches. Relative to standard model‐based methods, novel objective functional connectivity analyses may offer improved sensitivity to subtle changes in the distribution of memory functions relevant for surgical planning in TLE. Hum Brain Mapp, 2009. © 2009 Wiley‐Liss, Inc.     

Hubs disruption in mesial temporal lobe epilepsy. A resting‐state fMRI study on a language‐and‐memory network

Mesial temporal lobe epilepsy (mTLE) affects the brain networks at several levels and patients suffering from mTLE experience cognitive impairment for language and memory. Considering the importance of language and memory reorganization in this condition, the present study explores changes of the embedded language‐and‐memory network (LMN) in terms of functional connectivity (FC) at rest, as measured with functional MRI. We also evaluate the cognitive efficiency of the reorganization, that is, whether or not the reorganizations support or allow the maintenance of optimal cognitive functioning despite the seizure‐related damage. Data from 37 patients presenting unifocal mTLE were analyzed and compared to 48 healthy volunteers in terms of LMN‐FC using two methods: pairwise correlations (region of interest [ROI]‐to‐ROI) and graph theory. The cognitive efficiency of the LMN‐FC reorganization was measured using correlations between FC parameters and language and memory scores. Our findings revealed a large perturbation of the LMN hubs in patients. We observed a hyperconnectivity of limbic areas near the dysfunctional hippocampus and mainly a hypoconnectivity for several cortical regions remote from the dysfunctional hippocampus. The loss of FC was more important in left mTLE (L‐mTLE) than in right (R‐mTLE) patients. The LMN‐FC reorganization may not be always compensatory and not always useful for patients as it may be associated with lower cognitive performance. We discuss the different connectivity patterns obtained and conclude that interpretation of FC changes in relation to neuropsychological scores is important to determine cognitive efficiency, suggesting the concept of “connectome” would gain to be associated with a “cognitome” concept.     

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.     

Possible remote functional reorganization in left temporal lobe epilepsy

Objective –  To provide functional magnetic resonance imaging-based insight into the impact of left temporal lobe epilepsy (TLE) on language-related functional re-organization.
Materials and methods –  Ten right-handed patients with left TLE were compared with 10 matched healthy controls. Regional brain activation during the language task was measured in the inferior frontal gyrus (IFG) and in the superior temporal gyrus (STG), and the regional inter-hemispheric lateralization index (LI) was calculated.
Results –  Left language lateralization was documented in all the patients and controls. Reduced lateralization in the IFG was due to decreased activity in the left frontal region rather than to increased activity in the right frontal region. The LI values in the STG correlated with the LI values in the IFG in the controls but not in the patients.
Conclusions –  The left IFG was most probably involved in the epileptogenesis and concomitant language-related cortical plasticity in patients with left TLE.     

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.     

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.     

The relationship between glucose metabolism,resting-state fMRI BOLD signal,and GABAA-binding potential: a preliminary study in healthy subjects and those with temporal lobe epilepsy

Glucose metabolism has been associated with magnitude of blood oxygen level-dependent (BOLD) signal and connectivity across subjects within the default mode and dorsal attention networks. Similar correlations within subjects across the entire brain remain unexplored. [¹⁸F]-fluorodeoxyglucose positron emission tomography ([¹⁸F]-FDG PET), [¹¹C]-flumazenil PET, and resting-state functional magnetic resonance imaging (fMRI) scans were acquired in eight healthy individuals and nine with temporal lobe epilepsy (TLE). Regional metabolic rate of glucose (rMRGlu) was correlated with amplitude of low frequency fluctuations (ALFFs) in the fMRI signal, global fMRI connectivity (GC), regional homogeneity (ReHo), and gamma-aminobutyric acid A–binding potential (GABA_A BP_ND) across the brain. Partial correlations for ALFFs, GC, and ReHo with GABA_A BP_ND were calculated, controlling for rMRGlu. In healthy subjects, significant positive correlations were observed across the brain between rMRGlu and ALFF, ReHo and GABA_A BP_ND, and between ALFFs and GABA_A BP_ND, controlling for rMRGlu. Brain-wide correlations between rMRGlu and ALFFs were significantly lower in TLE patients, and correlations between rMRGlu and GC were significantly greater in TLE than healthy subjects. These results indicate that the glutamatergic and GABAergic systems are coupled across the healthy human brain, and that ALFF is related to glutamate use throughout the healthy human brain. TLE may be a disorder of altered long-range connectivity in association with glutamate function.     

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.     

Delineating functional segregations of the human middle temporal gyrus with resting‐state functional connectivity and coactivation patterns

Although the middle temporal gyrus (MTG) has been parcellated into subregions with distinguished anatomical connectivity patterns, whether the structural topography of MTG can inform functional segregations of this area remains largely unknown. Accumulating evidence suggests that the brain's underlying organization and function can be directly and effectively delineated with resting‐state functional connectivity (RSFC) by identifying putative functional boundaries between cortical areas. Here, RSFC profiles were used to explore functional segregations of the MTG and defined four subregions from anterior to posterior in two independent datasets, which showed a similar pattern with MTG parcellation scheme obtained using anatomical connectivity. The functional segregations of MTG were further supported by whole brain RSFC, coactivation, and specific RFSC, and coactivation mapping. Furthermore, the fingerprint with predefined 10 networks and functional characterizations of each subregion using meta‐analysis also identified functional distinction between subregions. The specific connectivity analysis and functional characterization indicated that the bilateral most anterior subregions mainly participated in social cognition and semantic processing; the ventral middle subregions were involved in social cognition in left hemisphere and auditory processing in right hemisphere; the bilateral ventro‐posterior subregions participated in action observation, whereas the left subregion was also involved in semantic processing; both of the dorsal subregions in superior temporal sulcus were involved in language, social cognition, and auditory processing. Taken together, our findings demonstrated MTG sharing similar structural and functional topographies and provide more detailed information about the functional organization of the MTG, which may facilitate future clinical and cognitive research on this area.     

单侧颞叶癫痫患者双侧大脑半球间的功能协同性研究

目的研究单侧颞叶癫痫患者双侧大脑半球间同伦功能连接的变化。方法纳入左侧颞叶癫痫(left temporal lobe epilepsy,LTLE)21例、右侧颞叶癫痫患者(right temporal lobe epilepsy,RTLE)22例以及正常对照(normal control,NC)20例。采用体素-镜像同伦功能连接(voxel-mirrored homotopic connectivity,VMHC)方法分析数据,计算出各组VMHC改变的脑区。结果与NC组相比较,LTLE组双侧辅助运动区(t=-3.35)、颞中回(t=-3.50)、内侧额上回(t=-3.20)、顶下小叶(t=-3.66)VMHC值降低;双侧角回(t=3.03)、枕下回(t=4.25)、顶上回(t=3.62)VMHC值升高(P0.05,alphasim校正)。与NC组相比较,RTLE组双侧颞中回(t=-4.26)、中央前回(t=-3.29)VMHC值减低;双侧枕下回(t=3.22)、海马旁脑回(t=3.32)和小脑(t=3.50)VMHC值升高(P0.05,alphasim校正)。结论单侧颞叶癫痫患者两侧半球间部分脑区的功能协同性发生了变化。     

Resting state functional connectivity of networks associated with reward and habit in anorexia nervosa

Neurobiological disturbances associated with reward and/or habit learning are theorized to maintain symptoms of anorexia nervosa (AN). Although research has investigated responses in brain regions associated with reward and habit to disorder‐specific cues (e.g., food) and presumed rewards (e.g., money), little is known about the functional organization of the circuits underlying these constructs independent of stimulus. This study aimed to provide initial data on the synchrony of networks associated with reward and habit in AN by comparing resting‐state functional connectivity (RSFC) patterns between AN and healthy control (HC) participants in these circuits and delineating how these patterns relate to symptoms. Using theoretically selected seeds in the nucleus accumbens (NAcc), ventral caudate, and dorsal caudate, reflecting a continuum from reward‐ to habit‐ oriented regions, RSFC patterns were compared between AN restricting subtype (n = 19) and HC (n = 19) participants (cluster threshold: p < .01). Exploratory correlations between RSFC z‐scores and Eating Disorder Examination (EDE) scores, BMI, and illness duration were conducted. The AN group demonstrated lower RSFC between the NAcc and superior frontal gyrus, between the ventral caudate and frontal and posterior regions, and between the dorsal caudate and frontal, temporal, and posterior regions. In the AN group, lower NAcc‐ superior frontal gyrus RSFC correlated with greater EDE Global scores (r = ?.58, CI: ?.83, ?.13). These resting‐state synchrony disruptions of the ventral and dorsal frontostriatal circuits, considered in context of the broader literature, support the utility of further investigating possible reward and habit disturbances supporting symptoms in AN.     

颞叶低级别肿瘤并顽固性癫痫的外科治疗策略

目的：分析颞叶低级别肿瘤并癫痫的临床特点,并探讨其手术治疗策略。方法回顾2013年1月至2014年1月27例颞叶低级别肿瘤并癫痫患者的临床资料,分析其临床特点、手术切除策略及术后疗效。结果全组病变部位分布于颞叶外侧、颞叶内侧、颞叶底面、颞后等各个区域,少数累及到颞叶以外脑区。发作首发症状分别为精神体验先兆、植物神经先兆、视幻觉、愣神、失语、自动运动、复杂运动甚至全面性强直发作等。27例中,病变手术全切除5例,扩大切除20例,次全切除2例。全组病例术后无严重并发症。发作控制：所有患者术后随访1年以上,仅1例次全切除者为EngelⅡ级,其余26例（96．3％）均为EngelⅠ级。结论颞叶低级别肿瘤并顽固性癫痫视病变部位及所累及致痫网络的不同而发作首症状表现各异;对颞叶低级别肿瘤并顽固性癫痫,应行严谨的术前评估致痫区与肿瘤的关系,周密设计切除计划,在保障安全前提下尽可能全切肿瘤以及充分切除致痫区,必要时结合神经导航、术中唤醒皮层电刺激功能区定位或颅内电极等技术;手术后发作控制效果佳。     

前颞叶和海马切除治疗难治性颞叶癫痫对认知功能影响的研究

目的 探讨前颞叶和海马切除治疗难治性颞叶癫痫对认知功能的影响.方法 19例难治性颞叶癫痫患者接受前颞叶和海马切除手术,手术前和手术后3、6月进行认知神经心理学测评以了解认知功能的变化.结果 19例难治件颞叶癫痫患者接受了前颞叶和海马切除术后取得了良好的疗效,术后1例有-过性的言语障碍,2例有-过性的欣快等精神症状.难治性颞叶癫痫患者存在严重的认知功能障碍(特别是智力、注意力、记忆功能障碍),前颞叶和海马切除手术没有加重认知功能障碍.在手术后6月一些认知功能反而有改善的趋势.结论 难治性颞叶癫痫患者存在认知功能障碍,采用前颞叶和海马切除能治愈或减少颞叶癫痫发作,并且对认知功能障碍有一定的改善作用.