Preoperative amygdala fMRI in temporal lobe epilepsy

Purpose:   Anterior temporal lobe resections (ATLR) benefit 70% of patients with refractory mesial temporal lobe epilepsy (TLE), but may be complicated by emotional disturbances. We used functional magnetic resonance imaging (fMRI) to investigate the role of the amygdala in processing emotions in TLE and whether this may be a potential preoperative predictive marker for emotional disturbances following surgery.
Methods:   We studied 54 patients with refractory mesial TLE due to hippocampal sclerosis (28 right, 26 left) and 21 healthy controls using a memory encoding fMRI paradigm, which included viewing fearful and neutral faces. Twenty-one TLE patients (10 left, 11 right) subsequently underwent ATLR. Anxiety and depression were assessed preoperatively and 4 months postoperatively using the Hospital Anxiety and Depression Scale.
Results:   On viewing fearful faces, healthy controls demonstrated left lateralized, while right TLE patients showed bilateral amygdala activation. Left TLE patients had significantly reduced activation in left and right amygdalae compared to controls and right TLE patients. In right TLE patients, left and right amygdala activation was significantly related to preoperative anxiety and depression levels, and preoperative right amygdala activation correlated significantly with postoperative change of anxiety and depression scores, characterized by greater increases in anxiety and depression in patients with greater preoperative activation. No such correlations were seen for left TLE patients.
Discussion:   The fearful face fMRI paradigm is a reliable method for visualizing amygdala activation in controls and patients with mesial TLE. Activation of the right amygdala preoperatively was predictive of emotional disturbances following right ATLR.     

Intracarotid amobarbital procedure and prediction of postoperative memory in patients with left temporal lobe epilepsy and hippocampal sclerosis

PURPOSE: Although temporal lobe epilepsy (TLE) patients with dominant hemisphere hippocampal sclerosis generally have good cognitive outcome after anterior temporal lobectomy (ATL), a minority of patients experience at least mild post-ATL decline on one or more standardized measures of episodic and semantic memory. The goal of this investigation was to determine whether memory outcome in this group could be predicted from preoperative intracarotid amobarbital procedure (IAP) recognition memory scores. METHODS: Data from 22 left TLE patients were studied retrospectively. All were left hemisphere language dominant and had IAP scores for each hemisphere, a significant degree of pathology-confirmed left hippocampal sclerosis (HS+), and no positive MRI findings other than atrophy. Cognitive outcome status was represented by the number of pre- to post-ATL declines across three tests, as defined by 90th percentile Reliable Change Index (RCI) criteria. RESULTS: Only 14% of the sample exhibited decline on more than one memory test. Low right IAP (left hemisphere injection) scores and relatively high preoperative cognitive ability and age at surgery predicted a greater risk of post-ATL memory decline. CONCLUSIONS: A minority of left TLE HS+ patients experience at least a mild degree of RCI-defined decline in episodic or semantic memory after ATL. The right hemisphere IAP memory score, which reflects the functional reserve of the contralateral hemisphere, can help predict the risk of postoperative memory decline for TLE patients in whom HS+ is likely based on the presence of hippocampal atrophy on MRI or early age of seizure onset.     

Significance of lateralization of upper limb automatisms in temporal lobe epilepsy: A quantitative movement analysis

Purpose: To evaluate the significance of lateralization of ictal upper limb automatisms in patients with temporal lobe epilepsy (TLE). Methods: Ictal upper limb automatisms of 28 patients with temporal lobe epilepsy were quantified. Duration of automatisms in relation to total seizure duration, movement speed, extent, length, and predominant frequencies of the movements were analyzed for both upper extremities separately and compared to the lateralization of the epileptogenic temporal lobe. Results: Predominantly ipsilateral upper limb automatisms were more common (n = 19) than predominantly contralateral automatisms (n = 9). The duration of ictal ipsilateral upper limb automatisms was significantly longer than the duration of contralateral automatisms (ipsilateral automatisms: 29 of 86 s total seizure duration; contralateral automatisms: 19 of 110 s total seizure duration; p = 0.048). Patients with ipsilateral upper limb automatisms had more often exclusively unitemporal interictal epileptiform discharges (IEDs) (84.2%) than patients with contralateral automatisms (11.1%; p < 0.001). The positive predictive value (PPV) of the combination of these parameters is 84.2%. Excellent surgical seizure outcome was better in patients with ipsilateral upper limb automatisms (77.8%) compared to those with contralateral automatisms (20%) (p = 0.09). The quantitative analysis of movement extent, average speed, maximum speed, and repetition rate of ipsilateral and contralateral upper limb automatisms did not show any statistically significant difference in this patient sample. Conclusion: The lateralization of upper limb automatisms in TLE has a good lateralizing value if the lateralization of IEDs were also taken into consideration.     

丙泊酚Wada试验与功能磁共振在颞叶癫痫词汇记忆功能偏侧化评估中的应用

目的 比较丙泊酚Wada试验与功能磁共振(fMRI)在左颞叶癫痫患者术前记忆功能偏侧化预测中的一致性和敏感性. 方法 对广州军区广州总医院自2009年10月至2011年10月收治的8例左前颞叶切除的癫痫患者术前进行丙泊酚Wada试验和fMRI记忆功能偏侧化评估,结合韦氏记忆测验结果,比较两者记忆功能偏侧化评估的一致性与预测记忆变化的敏感性. 结果 fMRI词汇记忆半球、内侧颞叶功能偏侧化与Wada试验功能偏侧化判定的一致率分别为57.0％和71.4％,术后记忆商数、词汇匹配以及智力改变与fMRI词汇记忆内侧颞叶功能偏侧化指数呈显著相关(r=-0.314,P=0.037;r=-0.387,P=.013;r=0.116,P=0.020),与Wada试验功能偏侧化指数无相关性(r=-0.442,P=.077;r=-0.241,P=0.237;r=-0.070,P=0.107). 结论 丙泊酚Wada试验和fMRI记忆功能偏侧化评估一致性因感兴趣区选择方法不同而不同.相对于Wada试验,fMRI记忆功能偏侧化指数在预测患者术后词汇记忆下降的过程中敏感性更高.     

Language lateralization in female patients with schizophrenia: an fMRI study

Gender differences in schizophrenia are among the most consistently reported findings in schizophrenia research. However, the biological substrate underlying these gender differences is still largely unknown. Differences in language lateralization between men and women may underlie some gender differences in schizophrenia.

In previous functional imaging studies, language lateralization was found to be decreased in male schizophrenia patients as compared to healthy males, which was due to enhanced language activation of the right hemisphere as compared to the healthy males. It could be hypothesized that decreased language lateralization in schizophrenia is gender specific, i.e. decreased lateralization in male patients and normal lateralization in female patients.

To test this hypothesis, language activation was measured in 12 right-handed female patients with schizophrenia and 12 healthy females, and compared to findings in 12 male patients and 12 male controls of an earlier study.

Language lateralization was significantly lower in the female patients (0.44) as compared to the female controls (0.75), which was due to increased activation of the right-sided language areas (patients: 19 voxels; controls: 8 voxels), while left hemisphere activation was similar in patients and controls. When these data are compared to the male patients and controls, both patient groups had lower lateralization than their healthy counterparts, but there was no difference between male and female patients. In both sexes, decreased lateralization resulted from increased right hemispheric language activation, which suggests a failure to inhibit nondominant language areas in schizophrenia. These findings indicate that lower language lateralization in women is not likely to underlie gender differences in schizophrenia.     

The localization and lateralization of memory deficits in children with temporal lobe epilepsy

PURPOSE: It is often reported that children with temporal lobe epilepsy (TLE) experience nonlateralized memory impairments. However, many of these studies have been exploratory and not based on memory theory. Further, differences between mesial and lateral subgroups have not been adequately examined. This study aimed to discern more specific patterns of memory impairment in children with TLE. METHODS: Forty-three children (5-16 years) with lesional TLE participated. Subjects were categorized in terms of lesion laterality (left, n = 21; right, n = 22) and intratemporal location (mesial, n = 31; lateral, n = 12). Verbal and nonverbal memory tasks were administered that reflected associative, allocentric and recognition paradigms. RESULTS: Facial recognition was poorer in right TLE (p = 0.03). There were no differences between left and right groups on any other memory task, even when comparisons were restricted to cases with mesial involvement. Irrespective of laterality, clear differences were observed between mesial and lateral lesion subgroups (arbitrary associative learning, p = 0.01; complex figure recall, p = 0.03). The lateral lesion subgroup displayed intact memory function relative to normative standards. CONCLUSIONS: Memory is more frequently impaired in children with mesial as opposed to lateral TLE. Tasks with an associative component discriminated between these subgroups, supporting an associative model of hippocampal function. With the exception of facial recognition, memory deficits were not lateralized. Therefore, the nature of memory impairment experienced by children with TLE cannot be extrapolated from adult models.     

Metabolic evidence for episodic memory plasticity in the nonepileptic temporal lobe of patients with mesial temporal epilepsy

Purpose: Metabolic changes have been described in the nonepileptic temporal lobe of patients with unilateral mesiotemporal lobe epilepsy (MTLE) associated with hippocampal sclerosis (HS). To better understand the functional correlate of this metabolic finding, we have sought to characterize brain regions in patients with MTLE that show correlation between unilateral episodic memory performances, as assessed by intracarotid amobarbital test (IAT), and interictal regional cerebral metabolism measured by [¹⁸F]‐fluorodeoxyglucose positron emission tomography (FDG‐PET). Methods: Resting FDG‐PET was performed interictally in 26 patients with unilateral MTLE caused by HS (16 female, mean age: 36 years; 16 left HS). Using statistical parametric mapping (SPM8), we performed a group comparison analysis comparing brain metabolism in the patients and in 54 adult controls (27 female, mean age: 32 years), with FDG‐PET data of right HS patients being flipped. IAT scores of nonepileptic hemisphere functions (amobarbital injection ipsilateral to HS) were used as covariates of interest in a correlation analysis with regional brain metabolism. Key Findings: The group comparison analysis revealed significant hypometabolic areas in a widespread temporofrontal network ipsilateral to HS. In addition, a significant increase in metabolism was found in mesial and lateral temporal regions contralateral to HS. Significant positive correlations were found between IAT scores of nonepileptic hemisphere functions and mesial temporal metabolism in this hemisphere. Significance: This study demonstrates the existence of significant increase in relative regional cerebral glucose metabolism in mesial and lateral temporal regions contralateral to the epileptic focus in patients with unilateral MTLE associated with HS. The positive correlation in these brain regions between IAT scores and metabolism supports the role of disease‐induced plasticity mechanisms contralateral to HS in the preservation of episodic memory processes.     

Postoperative memory prediction in left temporal lobe epilepsy: The Wada test is of no added value to preoperative neuropsychological assessment and MRI

The contribution of the Wada test (intracarotid amytal procedure, IAP) to predicting postoperative memory outcome in left temporal lobe epilepsy (LTLE) is becoming increasingly controversial when preoperative neuropsychological evaluation and MRI findings are available. We retrospectively analyzed 59 patients with LTLE who underwent en bloc temporal lobe resection. All patients had valid bilateral IAP test results, complete pre- and postoperative neuropsychological evaluation, and MRI grading on a 5-point scale integrating T 2 signal increase and degree of atrophy. Thirty percent of patients showed postoperative memory decline. Multiple regression analysis revealed that significant predictors of decline [F(2.56) = 22.71, P < 0.001, r² = 0.448] included preoperative memory learning score [t = −5.89, P < 0.001] and MRI classification [t = 3.10, P < 0.003], but not IAP scores. The IAP is of no added value in the prediction of postoperative memory outcome in LTLE in the presence of comprehensive neuropsychological and MRI data.     

Language lateralization in temporal lobe epilepsy using functional MRI and probabilistic tractography

Purpose: Language functional magnetic resonance imaging (fMRI) is used to noninvasively assess hemispheric language specialization as part of the presurgical work-up in temporal lobe epilepsy (TLE). White matter asymmetries on diffusion tensor imaging (DTI) may be related to language specialization as shown in controls and TLE. To refine our understanding of the effect of epilepsy on the structure–function relationships, we focused on the arcuate fasciculus (ArcF) and the inferior occipitofrontal fasciculus (IOF) and tested the relationship between DTI- and fMRI-based lateralization indices in TLE.
Methods: fMRI with three language tasks and DTI were obtained in 20 patients (12 right and 8 left TLE). The ArcF, a major language-related tract, and the IOF were segmented bilaterally using probabilistic tractography to obtain fractional anisotropy (FA) lateralization indices. These were correlated with fMRI-based lateralization indices computed in the inferior frontal gyrus (Pearson's correlation coefficient).
Results: fMRI indices were left-lateralized in 16 patients and bilateral or right-lateralized in four. In the ArcF, FA was higher on the left than on the right side, reaching significance in right but not in left TLE. We found a positive correlation between ArcF anisotropy and fMRI-based lateralization indices in right TLE (p < 0.009), but not in left TLE patients. No correlation was observed for the IOF.
Conclusions: Right TLE patients with more left-lateralized functional activations also showed a leftward-lateralized arcuate fasciculus. The decoupling between the functional and structural indices of the ArcF underlines the complexity of the language network in left TLE patients.     

Language lateralization in individuals with callosal agenesis: an fMRI study

Since the seminal work of Broca in 1861, it is well established that language is essentially processed in the left hemisphere. However, the origin of hemispheric specialization remains controversial. Some authors posit that language lateralization is genetically determined, while others have suggested that hemispheric specialization develops with age. Tenants of the latter view have further suggested that the adult pattern of left hemispheric specialization is achieved by means of callosal inhibition of homologous speech areas in the right hemisphere during ontogeny. According to this hypothesis, one would expect language to develop bilaterally in the acallosal brain. A recent functional magnetic resonance imaging (fMRI) study in one patient with agenesis of the corpus callosum suggests that this might indeed be the case (Riecker et al., 2007). However, given the large anatomic and functional variability in the population of subjects with agenesis of the corpus callosum, this finding needs to be more extensively replicated. In the present study, we explored language lateralization in six individuals with agenesis of the corpus callosum using an fMRI protocol which included a syntactic decision task and a sub-vocal verbal fluency task. Two neurologically intact control groups, one comparable to the acallosals in terms of IQ, age and education (n = 6) and one group with a high IQ (n = 5), performed the same tasks. No differences were found between language lateralization of the subjects with agenesis of the corpus callosum and the control groups in the receptive speech task. However, for expressive speech, the groups differed with respect to frontal activations, with the acallosal participants showing a more bilateral pattern of activation than the high-IQ participants only. No differences were found for temporal regions. Overall, these results indicate that the corpus callosum is not essential for the establishment of lateralized language functions.     

Bringing memory fMRI to the clinic: Comparison of seven memory fMRI protocols in temporal lobe epilepsy

fMRI is increasingly implemented in the clinic to assess memory function. There are multiple approaches to memory fMRI, but limited data on advantages and reliability of different methods. Here, we compared effect size, activation lateralisation, and between‐sessions reliability of seven memory fMRI protocols: Hometown Walking (block design), Scene encoding (block design and event‐related design), Picture encoding (block and event‐related), and Word encoding (block and event‐related). All protocols were performed on three occasions in 16 patients with temporal lobe epilepsy (TLE). Group T‐maps showed activity bilaterally in medial temporal lobe for all protocols. Using ANOVA, there was an interaction between hemisphere and seizure‐onset lateralisation (P = 0.009) and between hemisphere, protocol and seizure‐onset lateralisation (P = 0.002), showing that the distribution of memory‐related activity between left and right temporal lobes differed between protocols and between patients with left‐onset and right‐onset seizures. Using voxelwise intraclass Correlation Coefficient, between‐sessions reliability was best for Hometown and Scenes (block and event). The between‐sessions spatial overlap of activated voxels was also greatest for Hometown and Scenes. Lateralisation of activity between hemispheres was most reliable for Scenes (block and event) and Words (event). Using receiver operating characteristic analysis to explore the ability of each fMRI protocol to classify patients as left‐onset or right‐onset TLE, only the Words (event) protocol achieved a significantly above‐chance classification of patients at all three sessions. We conclude that Words (event) protocol shows the best combination of between‐sessions reliability of the distribution of activity between hemispheres and reliable ability to distinguish between left‐onset and right‐onset patients. Hum Brain Mapp 36:1595–1608, 2015. © 2015 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc.     

颞叶癫痫的磁共振波谱学定侧研究

目的　探讨磁共振波谱学 (magneticResonanceSpectroscopy ,MRS)在颞叶癫痫术前定位中的作用。方法　取 18例接受手术治疗的顽固性颞叶癫痫患者为研究对象 ,其术前已接受EEG、MRI和PET等检查获得定位。接受双侧颞叶内侧的MRS检查 ,测定其N -乙酰天门冬氨酸 (NAA)、肌酐 (Cr)和胆碱 (Cho)含量 ,并计算NAA/(Cr Cho)的比值 ;以NAA/(Cr Cho) <0 .6 8和双侧NAA/(Cr Cho)比值的差别 >7%为标准。结果　在18例病例中 16例患侧颞叶MRS检查结果异常 ,其中 9例为患侧MRS异常 ,7例为双侧MRS异常 ,以患侧为重 ,2例患者的比值正常 ;MRS的敏感性高于MR(15 /18) ,与MR结合 ,可对 17例患者进行术前定侧。结论　MRS对颞叶癫痫的定侧诊断有较高的准确性 ,为颞叶癫痫的定位诊断提供新的手段 ;与MRI、PET等手段结合使用 ,可进一步提高对颞叶癫痫诊断的敏感性和准确性     

Clinical seizure lateralization in frontal lobe epilepsy

PURPOSE: We systematically analyzed the lateralizing value of clinical seizure semiology in patients with frontal lobe epilepsy (FLE). METHODS: We studied the incidence, positive predictive value (PPV), and the lateralizing significance of various clinical symptoms in 228 seizures (s) of 31 patients (p) with medically refractory FLE (17 with left-sided and 14 with right-sided seizure onset). Seizures recorded during prolonged video-EEG monitoring were assessed by two independent reviewers blinded for the patient's clinical data. Analysis was performed both for patients and seizures. RESULTS: Version [16 p (52%); PPV, 94%; p=0.001; 47 s (21%); PPV, 75%; p=0.001], unilateral clonic movements [16 p (52%); PPV, 81%; p=0.021; 32 s (14%); PPV, 81%; p=0.001], unilateral dystonic posturing [eight p (26%); PPV, 75%; p=0.289; 46 s (20%); PPV, 80%; p=0.001], unilateral tonic posturing [10 p (32%); PPV, 80%; p=0.109; 19 s (7.4%); PPV, 79%; p=0.019], and unilateral grimacing [10 p (32%); PPV, 100%; p=0.002; 19 s (8%); PPV, 100%; p=0.001] were of lateralizing significance, indicating a contralateral seizure onset. Asymmetric ending [five p (16%); PPV, 80%; p=0.375; nine s (4%); PPV, 89%; p=0.039] after secondarily generalized tonic-clonic seizures was significantly associated with an ipsilateral seizure onset. Pure ictal vocalizations occurred significantly more frequently in seizures of right hemispheric onset [13 p (42%); PPV, 62%; p=0.581; 63 s (28%); PPV, 73%; p=0. 001], whereas in individual patients, this symptom showed no lateralizing significance. The remaining clinical symptoms (figure 4 sign, unilateral hand automatisms, early head turning, postictal nose wiping, and unilateral eye blinking) were not of lateralizing significance in our patients. The results of clinical seizure lateralization corresponded with the final lateralization of the seizure-onset zone in 81% of our patients. CONCLUSIONS: Clinical seizure semiology can provide correct information on the lateralization of the seizure-onset zone in >80% of patients with medically refractory frontal lobe epilepsy.     

Language lateralization correlates with verbal memory performance in children with focal epilepsy

Purpose: Assessment of language dominance with functional magnetic resonance imaging (fMRI) and neuropsychological evaluation is often used prior to epilepsy surgery. This study explores whether language lateralization and cognitive performance are systematically related in young patients with focal epilepsy. Methods: Language fMRI and neuropsychological data (language, visuospatial functions, and memory) of 40 patients (7–18 years of age) with unilateral, refractory focal epilepsy in temporal and/or frontal areas of the left (n = 23) or right hemisphere (n = 17) were analyzed. fMRI data of 18 healthy controls (7–18 years) served as a normative sample. A laterality index was computed to determine the lateralization of activation in three regions of interest (frontal, parietal, and temporal). Results: Atypical language lateralization was demonstrated in 12 (30%) of 40 patients. A correlation between language lateralization and verbal memory performance occurred in patients with left‐sided epilepsy over all three regions of interest, with bilateral or right‐sided language lateralization being correlated with better verbal memory performance (Word Pairs Recall: frontal r = ?0.4, p = 0.016; parietal r = ?0.4, p = 0.043; temporal r = ?0.4, p = 0.041). Verbal memory performance made the largest contribution to language lateralization, whereas handedness and side of seizures did not contribute to the variance in language lateralization. Discussion: This finding reflects the association between neocortical language and hippocampal memory regions in patients with left‐sided epilepsy. Atypical language lateralization is advantageous for verbal memory performance, presumably a result of transfer of verbal memory function. In children with focal epilepsy, verbal memory performance provides a better idea of language lateralization than handedness and side of epilepsy and lesion.     

Comparison of the intracarotid amobarbital procedure and interictal cerebral 18-fluorodeoxyglucose positron emission tomography scans in refractory temporal lobe epilepsy.

The relationship between interictal focal hypometabolism determined by 18-fluorodeoxyglucose positron emission tomography (FDG-PET) scans and memory function with the intracarotid amobarbital procedure (IAP) was evaluated in 23 patients with temporal lobe epilepsy. All patients underwent prolonged EEG/video monitoring. The epileptogenic focus was defined by interictal epileptiform discharges and ictal onsets. All 23 patients had recorded seizures arising exclusively from one temporal lobe. PET showed temporal lobe hypometabolism ipsilateral to the epileptogenic focus in 86% (20 of 23) of patients; IAP showed impaired memory of the hemisphere of seizure onset in 65% (15 of 23). Sixty-five percent (13 of 20) of patients with focal hypometabolism had ipsilateral memory impairment. Memory impairment contralateral to the hypometabolic zone was not observed. Ninety-five percent (22 of 23) of patients demonstrated functional impairment by either PET or IAP (or both) on the epileptogenic side.     

Depression in temporal lobe epilepsy surgery patients: an FDG-PET study

PURPOSE: Depression is common in temporal lobe epilepsy (TLE) and after temporal lobectomy, and its etiology is obscure. In nonepileptic depression (including depression associated with other neurologic disorders), a consistent PET imaging finding is frontal lobe hypometabolism. Many TLE patients have hypometabolism involving frontal regions. Thus in data available from routine clinical assessments in an epilepsy surgery unit, we tested the hypothesis that the pattern of hypometabolism, particularly in the frontal lobe, may be associated with the depression seen in patients with TLE and TLE surgery. METHODS: We studied 23 medically refractory TLE patients who underwent anterior temporal lobectomy and who had preoperative FDG-PET scanning. All patients had pre- and postoperative psychiatric assessment. By using statistical parametric mapping (SPM-99), patterns of hypometabolism were compared between patients who had a preoperative history of depression (n=9) versus those who did not (n=14) and between those in whom postoperative depression developed (n=13) versus those in whom it did not (n=10). A significant region of hypometabolism was set at p<0.001 for a cluster of >or=20 contiguous voxels. RESULTS: Patients with a history of depression at any time preoperatively showed focal hypometabolism in ipsilateral orbitofrontal cortex compared with those who did not (t=4.64; p<0.001). Patients in whom depression developed postoperatively also showed hypometabolism in the ipsilateral orbitofrontal region (t=5.10; p<0.001). CONCLUSIONS: Although this study is methodologically limited, and other explanations merit consideration, orbitofrontal cortex dysfunction, already implicated in the pathophysiology of nonepileptic depression, may also be relevant to the depression of TLE and temporal lobectomy.     

Left-sided interictal epileptic activity induces shift of language lateralization in temporal lobe epilepsy: an fMRI study

PURPOSE: By using speech-activated functional MRI (fMRI), we investigated whether the frequency of left-sided interictal epileptic activity (IED: spikes or sharp waves on the EEG) is associated with atypical speech lateralization. METHODS: We investigated 28 patients (13 men, aged 17-59 years) with left-sided mesial temporal lobe epilepsy (MTLE) and 11 patients with right-sided MTLE as a control population. Only patients with unilateral hippocampal sclerosis with unilateral IED were included. For fMRI of individual patients, we contrasted images sampled during covert word generation with a low-level rest condition. With SPM99, an individual comparison for the contrast "word generation versus resting inactivity" was conducted. To characterize speech lateralization in individual patients, we calculated asymmetry indexes (AIs): the difference between activated left-sided and right-sided voxels was divided by all activated voxels. Analyzing long-term EEG, the first 2 min of each hour were evaluated for the frequency of IED. Univariate associations with AIs were assessed by Pearson's correlation and by t test. When testing the independent associations, multivariate linear regression was performed. RESULTS: The AIs in patients with left-sided MTLE were 0.40 +/- 0.53 on average (range, -0.83 to +1.0), whereas in right-sided MTLE, they were 0.78 +/- 0.15 (p = 0.029). For the further investigations, we included left-sided MTLE patients only. The median frequency of IED was six per hour (range, 0-240). Higher IED frequency was correlated with left-right shift of lateralization of speech fMRI activity (p = 0.002). CONCLUSIONS: Higher left-sided spike frequency in MTLE was associated with a left-right shift of speech representation, suggesting that chronic frequent interictal activity may induce a reorganization of speech lateralization.