Predictors of atypical language lateralization in focal epilepsy: A mega‐analysis of fMRI evidence

Freya Prentice; Lara Chehabeddine; Maria Helena Eriksson; Jennifer Murphy; Leigh N Sepeta; William D Gaillard; Madison M Berl; Frédérique Liégeois; Torsten Baldeweg

doi:10.1111/epi.18422

. 2025 May 5;66(8):2842–2852. doi: 10.1111/epi.18422

Predictors of atypical language lateralization in focal epilepsy: A mega‐analysis of fMRI evidence

Freya Prentice ^1,^2,^✉, Lara Chehabeddine ^1,^3,⁴, Maria Helena Eriksson ^1,^2,⁵, Jennifer Murphy ⁶, Leigh N Sepeta ⁷, William D Gaillard ⁷, Madison M Berl ^8,⁹, Frédérique Liégeois ¹, Torsten Baldeweg ^1,²

PMCID: PMC12371624 PMID: 40321151

Abstract

Objective

To identify predictors of language lateralization derived from functional magnetic resonance imaging (fMRI) in children and adults with left‐ and right‐sided focal epilepsy.

Methods

We conducted a mega‐analysis of data from 914 individuals from 24 samples. We used multilevel models to identify predictors of language lateralization in left and right hemisphere epilepsy groups. We assigned each participant a clinical predictor score to explore whether there was a cumulative influence of predictors on increasing atypical language lateralization.

Results

Left hemisphere epilepsy was a predictor of greater atypical language lateralization in the combined sample. Additional predictors of atypical language lateralization included left/ambidextrous handedness in both the left and right hemisphere groups, and longer duration of epilepsy, frontal lobe involvement, and history of a stroke or other precipitating injury in the left hemisphere group only. There was a cumulative effect of predictors in the left hemisphere groups. Eighty percent of individuals with four or more predictors had atypical language lateralization, compared to 19% of individuals with no predictors, other than left hemisphere epilepsy.

Significance

Consistent with theories of language plasticity, we demonstrated a robust effect of early acquired left hemisphere injury on language lateralization. There was also a subtle effect of duration of epilepsy, perhaps reflecting increasing bilaterality with age in adulthood. The association between left/ambidextrous handedness and atypical language lateralization in the left and right hemisphere groups likely reflects both genetic and epilepsy‐associated effects. The total number of predictors identified for an individual could serve as an indication for presurgical language fMRI, when surgical management is considered.

Keywords: epilepsy surgery, fMRI, language lateralization, language plasticity

Key points.

In our mega‐analysis of 914 participants, we identified robust predictors of atypical language lateralization.
Atypical language lateralization was associated with epilepsy in the left hemisphere; however, it was still common in the right hemisphere epilepsy groups.
There was a robust effect of early left hemisphere acquired injury on atypical language lateralization, presumably reflecting the effects of early plasticity.
A longer duration of epilepsy was associated with atypical language lateralization, perhaps akin to the effect of health aging on increasing bilaterality.
The effect of predictors was cumulative, whereby the total number of predictors serves as an indicator of atypical language lateralization in individual patients.

1. INTRODUCTION

Children and adults with focal epilepsy show higher rates of right and bilateral patterns of language lateralization than those seen in the general population (25%–30% in focal epilepsy vs 5% in healthy controls), ¹ as identified using task‐based functional magnetic resonance imaging (fMRI). This higher prevalence of atypical language lateralization in individuals with focal epilepsy is presumed to reflect either the disruption of the typical trajectory of left language specialization ² , ³ or interhemispheric reorganization of language networks from the left hemisphere (LH) to the right hemisphere (RH). ⁴ , ⁵ , ⁶ Accordingly, atypical language lateralization has been associated with a seizure focus or epileptogenic lesion in the LH. ⁷ , ⁸ , ⁹ , ¹⁰ , ¹¹ , ¹²

There is converging evidence that atypical language lateralization is more common in individuals with an early as opposed to late onset of seizures. ⁶ , ¹³ , ¹⁴ , ¹⁵ This is also consistent with theories of language plasticity that predict that atypical language lateralization is more likely when an insult is sustained at an early age due to less specialization in language networks and greater potential for reorganization early in development. ³ , ⁵ , ¹⁶ , ¹⁷ In a recent meta‐analysis of more than 1000 individuals, we found a small but significant correlation between earlier age at seizure onset and atypical language lateralization (Prentice et al., preprint ¹⁸ ). Other studies have shown reorganization after early acquired insults predating the onset of seizures including stroke and other precipitating injuries. ¹⁹ , ²⁰ , ²¹ These findings all suggest a critical role of early plasticity in language lateralization in focal epilepsy.

Other potential predictors of language lateralization in epilepsy, distinct from the effects of early plasticity, include duration of epilepsy, ²² left and ambidextrous handedness, ⁶ , ²⁰ , ²³ a mesial temporal lobe focus ²⁴ including hippocampal sclerosis (HS), ²⁵ structural asymmetries26, 27 and interictal epileptiform discharges. ⁹ However, only a few studies have examined how such variables interact to affect language lateralization, and these studies have been limited to temporal lobe epilepsy samples ²³ or studies with small sample sizes (n < 50). ²² A study on a small sample of adults with left HS identified predictors of atypical language lateralization (determined by Wada test) and demonstrated that a greater number of predictors was predictive of atypical language lateralization, suggesting that there may be a cumulative effect of those variables on language lateralization. ²¹

There is a need to identify predictors of language lateralization in a large and heterogenous focal epilepsy cohort. A 2017 study found that 50% of European epilepsy centers using fMRI for language lateralization recommended patients for presurgical fMRI if atypical language lateralization was suspected. ²⁸ Given that clinical indicators of atypical language lateralization are currently used in the selection of candidates for presurgical fMRI, identification of predictors of language lateralization could improve selection of candidates. In addition, some individuals are unable to complete a successful fMRI, and so in these cases, prediction of language lateralization from clinical variables is especially pertinent.

Here we conducted a mega‐analysis of 914 individuals with focal epilepsy to identify predictors of language lateralization and examine the cumulative influence of such predictors.

2. MATERIALS AND METHODS

2.1. Mega‐analysis dataset

The multicenter dataset used here was created as part of a previous meta‐analysis examining the association between age at seizure onset and language lateralization. ¹⁸ We carried out a literature search on August 14 2024, and we screened articles that included (1) individual with epilepsy and (2) fMRI for language lateralization. Screening resulted in the inclusion of 33 articles plus two additional pediatric datasets. Where data were available in the article or supplement, we extracted fMRI laterality indices (LIs) and clinical characteristics. Where data were not available, we requested them from the authors. Information on the side of epilepsy, age at seizure onset, and LIs were available for 1157 individuals across 35 samples. For this study specifically, we excluded samples with missing information on the localization of epilepsy, handedness, duration of epilepsy, and etiology. This resulted in a final sample of 914 individuals from 24 samples, BA including 646 with LH epilepsy and 268 with RH epilepsy. More detail on the methods for the search, screening, and data extraction can be found in the preprint. ¹⁸ A table containing the characteristics of each sample included in this study can be found in the Data S1.

2.2. Measures

2.2.1. Laterality indices

We used continuous LIs calculated from task‐based fMRI as a measure of language lateralization. LIs range from +1 to −1, indicating left to right language lateralization. LIs from the different samples were calculated using different language tasks and region of interest (ROI). Language tasks used for the LIs selected included verbal fluency (phonemic and semantic fluency, verb generation), auditory description, semantic decision, and a conjunction of multiple tasks. For those studies that reported LIs for multiple tasks, we chose tasks that robustly activated frontal regions, such as verbal fluency. Similarly, where studies reported LIs for multiple ROIs, we chose frontal ROIs, which have been shown to be reproducible ²⁹ and robust lateralizing ³⁰ in healthy adults. The language and baseline task and ROI used for each sample can be found in Table S1. In a sub‐analysis, we looked at predictors of language lateralization using LIs calculated in temporal ROI only, using receptive language tasks expected to produce appropriate temporal lobe activation (i.e., excluding fluency tasks). For descriptive statistics, LIs were categorized into right (−1 to −.2), bilateral (−.2 to .2), and left language representation (.2 to +1).

2.2.2. Predictor variables

All included participants had information on age at seizure onset, duration of epilepsy, side of epilepsy, location of epilepsy, pathology of epilepsy, handedness, and a history of insults predating the onset of seizures. We coded individuals as having LH or RH epilepsy and excluded those with no side of epilepsy reported or those with bilateral epilepsy. We coded whether the structural abnormality involved the frontal or temporal lobes. We coded scans that were reported as “MRI negative” as not having any known lobar location, irrespective of seizure focus.

Handedness was determined in several different ways across samples: using the Edinburgh Handedness Inventory or by clinical evaluation or self‐report. The method used by each sample can be seen in Table S1. Individuals were coded as being right‐handed vs left‐handed or ambidextrous. We categorized insults predating seizure onset into two separate groups: stroke and other precipitating injury, which included febrile seizures, infection, and head trauma.

2.3. Analysis strategy

2.3.1. Identification of predictors of language lateralization

Due to the negative skew in the residuals of these models we performed an exponential transformation of the LI values to reduce the skew. All statistical analyses used transformed LI values while the data visualization used untransformed LI values. As the data came from different samples we used a multilevel modeling approach, with the sample included as a random effect. Given that the different samples vary based on the language and baseline tasks used, ROI and LI calculation method, as well as the characteristics of the sample (see Table S1), “sample” best modeled the overall methodological variation. As fixed effects we included variables that have been previously associated with language lateralization: age at seizure onset, duration of epilepsy, handedness, HS diagnosis, stroke, other precipitating injuries, and the involvement of frontal or temporal regions, given their role in language functions.

In LH and RH samples separately, we entered all variables into a multilevel model, including sample as a random effect. We explored potential multicollinearity in the model by examining the Variance Inflation Factor (VIF). If the VIF was higher than 2 for one or more variables, we removed the variable with the highest VIF and reran the model. We repeated this procedure until all variables had a VIF under 2. We compared the Akaike information criteria (AIC) and Bayes factor (BF) of the final models with a model with random effects only, and ran chi‐square tests, to choose the model with best fit. In addition, we examined the interactions between side of epilepsy and all other variables in the combined sample, to determine whether predictors had a significantly different effect on language lateralization in the LH and RH epilepsy groups (see Data S1). We reran these analyses in a subset of the sample who also had temporal LIs (LH = 514, RH = 167).

2.3.2. Calculation of a “predictor score” for language lateralization

Variables that were found to be significant independent predictors in the final multilevel models were used to derive a cumulative “predictor score” for each individual in the LH and RH group. For example, if only a history of stroke and HS diagnosis were identified as significant predictors, and an individual had a history of stroke but no HS, they would receive a predictor score of 1. We used one‐way analyses of variance (ANOVAs) to compare the effect of “number of predictors” (i.e., an individual's predictor score) on language lateralization to examine whether there was a cumulative effect of predictors on increasingly right lateralized language. To examine significance with each additional predictor, we used post hoc pairwise comparison and applied the Benjamini–Hochberg correction.

2.3.3. Identification of predictors of left/ambidextrous handedness

Given that handedness has been previously identified as a predictor of language lateralization in both focal epilepsy ⁶ , ²⁰ , ²³ and in the general population, ³¹ , ³² and that rates of left handedness are greater in focal epilepsy populations, ³³ we also examined which epilepsy characteristics were associated with handedness beyond language lateralization. We used multilevel logistic regression models to examine the interaction between side of epilepsy and other included variables on handedness and applied the Benjamini–Hochberg correction to control for multiple comparison. The results of these analyses are presented in the Data S1.

3. RESULTS

3.1. Sample characteristics

The sample included 646 individuals with LH epilepsy and 268 with RH epilepsy. There were similar number of children (55%) and adults, and the median age at fMRI scan was 16.6 years (interquartile range [IQR] = 12.5–32.4). Most individuals had an onset of epilepsy in childhood (before 18 years; 82%), with a median age at seizure onset of 8.3 years (IQR = 4–14). Language tasks used for LI calculation included fluency (58%), auditory decision (22%), semantic decision (9%), or a conjunction of language tasks (6%), with all other tasks making up less than 5% of the sample. LI were calculated primarily using frontal ROI (80%), although some used a more extensive frontotemporal (17%) or whole brain ROI (3%). Handedness was determined primarily through clinical evaluation (51%), the Edinburgh Handedness Inventory or other standardized measures (28%), or self‐report (1%). For the other 20% of patients, the method of handedness determination was not specified. Descriptive statistics for the demographic and clinical characteristics of the LH and RH epilepsy samples can be found in Table 1.

TABLE 1.

Demographic and clinical characteristics of the LH and RH epilepsy samples.

	LH epilepsy sample	RH epilepsy samples
Age at fMRI scan, median [IQR]	17 years [12.7, 34]	16.1 years [11.8, 29.2]
Female sex, %	55%	56%
Age at seizure onset, median [IQR]	8 years [4, 14]	9 years [4, 13]
Duration of seizures, median [IQR]	7.95 years [3.9, 16]	7.58 years [3.95, 14]
Left/ambidextrous handedness, %	22%	16%
Frontal involvement, %	22%	20%
Temporal involvement, %	74%	74%
Hippocampal sclerosis diagnosis, %	36%	33%
Stroke, %	5%	1%
Other precipitating injury, %	17.5%	16%

Open in a new tab

Abbreviations: fMRI, functional magnetic resonance imaging; IQR, interquartile range; LH, left hemisphere; RH, right hemisphere.

3.2. Side of epilepsy

In the LH epilepsy sample, 34% of individuals had atypical language lateralization (20% right lateralized, 14% bilateral) and the median LI was .49 (IQR = −.08 to .73). In the RH epilepsy sample, 23% of individuals had atypical language lateralization (12% right lateralized, 11% bilateral) and the median LI was .61 (IQR = .25 to .80). In the combined LH and RH sample, LH epilepsy was a significant predictor of greater atypical language lateralization (β = −.22, p < .001).

3.3. Identification of predictors of language lateralization

For the LH multilevel model, the fixed effects explained 19% of the variance in LI, and the random effect explained an additional 3% (AIC = 1227). There was very strong evidence (BF > 1000) that this model was a better fit for the data than one with random effects only (AIC = 1302), and the difference was statistically significant (p < .001). Multicollinearity was low (VIF below 2). For the RH multilevel model, the fixed effects explained 7% of the variance in LI, and the random effects explained an additional 15% (AIC = 538). There was strong evidence (BF > 1000) that this model was a poorer fit for the data than one with random effects only (AIC = 510), and there was no statistically significant difference between the models (p > .05). Multicollinearity was low (VIF below 2). The estimates of the fixed effects for both the LH and RH epilepsy models are displayed in Table 2.

TABLE 2.

Estimates of fixed effects for LH and RH epilepsy sample multilevel models.

Model	Fixed effects	Estimate	t	p value
LH epilepsy	Age at seizure onset	−.00	−.20	.843
	Duration of epilepsy	−.01	−3.50	< .001^***
	Left/ambidextrous handedness	−.39	−6.39	< .001^***
	Frontal lobe involvement	−.16	−2.34	.019^**
	Temporal lobe involvement	.03	.39	.694
	Hippocampal sclerosis diagnosis	.05	.72	.471
	Stroke	−.45	−3.86	< .001^***
	Other precipitating injury	−.28	−4.14	< .001^***
RH epilepsy	Age at seizure onset	.01	1.76	.081
	Duration of epilepsy	.00	.24	.814
	Left/ambidextrous handedness	−.36	−3.55	< .001^***
	Frontal lobe involvement	.09	.88	.380
	Temporal lobe involvement	−.02	−.22	.825
	Hippocampal sclerosis diagnosis	.04	.36	.723
	Stroke	−.35	−1.01	.316
	Other precipitating injury	.04	.34	.731

Open in a new tab

Abbreviations: LH, left hemisphere; RH, right hemisphere.

p < .05.

^**

p < .01.

^***

p < .001.

Left/ambidextrous handedness was the only variable that was significantly predictive of atypical language lateralization in the final LH and RH models. Figure 1 shows the correlation between age at seizure onset and language lateralization in right vs left/ambidextrous handed individuals in the LH and RH epilepsy groups.

Distribution of language lateralization (laterality indices) and age at seizure onset in left/ambidextrous (yellow) and right‐handed individuals (turquoise) in the (A) left and right (B) hemisphere epilepsy groups.

In the subset of patients with LIs calculated in temporal ROI, left/ambidextrous handedness (β = −.20, p = .032) and stroke (β = −.35, p = .034) were the only significant predictors of temporal language lateralization in the LH epilepsy group, and there were no significant predictors in the RH epilepsy group. The full results of this analysis can be found in the Data S1.

3.4. Interactions with side of epilepsy

In the combined sample, there were significant interactions of LH epilepsy, with a longer duration of epilepsy (β = −.01, p = .026), frontal involvement (β = −.29, p = .030), and a history of precipitating injuries (β = −.44, p = .003) on language lateralization. These variables were associated with atypical language lateralization in the LH but not RH epilepsy groups. The interaction effects between side of epilepsy and all other variables can be found in the Data S1. Figure 2 shows the language lateralization patterns for those with LH and RH epilepsy, with the most common injuries reported to predate seizure onset: stroke, head trauma, febrile seizures, and encephalitis.

Language lateralization (laterality indices) in individuals with an insult predating seizure onset in the left (A) and right (B) hemisphere epilepsy groups.

3.5. Cumulative influence of predictor variables on language lateralization

In the LH sample, individuals could have up to five predictors (longer duration of epilepsy, left/ambidextrous handedness, frontal lobe involvement, stroke, or other precipitating injuries), although no individuals had all five predictors. Duration of epilepsy was coded categorically as “short” vs “long” using median duration for the total sample (≥7.8 years), given the lack of theoretical or empirical evidence for a cutoff above which duration of epilepsy has a greater effect. Eighty percent of those with four predictors were atypically lateralized, compared to 19% of those with zero predictors. Atypical language lateralization increased with the number of predictors (F (4, 641) = 32.92, p < .001). Post hoc comparisons showed that there was a difference in LI between groups with zero vs one predictor (p = .007), one vs two predictors (p < .001), and two vs three predictors (p = .008), but not three vs four predictors (p = .557) (see Figure 3A). In the RH sample, individuals could have one predictor (left/ambidextrous handedness); 46% of those with this predictor were atypically lateralized, compared to 20% of those with no predictors. There was an effect of the number of predictors on LI (F (1, 266) = 13, p < .001) (Figure 3B). When limiting the LH and RH sample to those with no predictors, LH epilepsy was no longer a significant predictor of atypical language lateralization in a multilevel model (β = −.004, p = .914).

Cumulative influence of the number of predictors on atypical language lateralization (laterality indices) in the left (A) and right (B) hemisphere samples and the percentage of individuals in each predictor score group with atypical language lateralization.

4. DISCUSSION

Our study identified predictors of fMRI language lateralization in a large focal epilepsy sample of 914 individuals, including both LH and RH epilepsy groups.

4.1. Acquired insults drive language reorganization

We found that a history of insults predating the onset of habitual seizures (including stroke) was an independent and robust predictor of greater atypical language lateralization in the LH group. It is possible that these early precipitating injuries may partially drive the previously demonstrated association between younger age at seizure onset and atypical language lateralization, ⁶ , ¹³ , ¹⁴ , ¹⁵ , ¹⁸ as seen with the inclusion of stroke patients in a previous study. ²⁰ Furthermore, the inclusion of these variables may explain why age at seizure onset was not a predictor of language lateralization in the final model for the LH group. Given that early theories of language plasticity were primarily based on children with early diffuse and hemispheric insults, ⁴ , ⁵ it is perhaps unsurprising that early acquired LH injury was a more robust predictor of reorganization than the age at seizure onset alone.

Our findings indicate that an acquired LH insult, such as a stroke or encephalitis, was associated with atypical language lateralization. It is possible that the higher rates of atypical language lateralisaiton in this group are due to both the sudden onset of acquired insults and more extensive damage to eloquent cortex compared to more focal and slow‐growing pathologies. Consistent with this, not all precipitating injuries had the same magnitude of effect on language lateralization, and in our multilevel model, stroke was the strongest predictor (Figure 2). As expected, early injury in the LH has a significantly greater effect on language lateralization than early RH injury. LH stroke was also a predictor of atypical language lateralization in the temporal lobe, suggesting that this type of early acquired injury is associated with extensive reorganization across frontal and temporal language regions. Overall, these findings demonstrate that acquired LH insults predating the onset of habitual seizures may be a key driver of language reorganization and serve, clinically, as an indicator for right or bilateral language representation.

4.2. Chronicity effect of seizures on language lateralization

Looking beyond the strong effect of an acquired injury on language reorganization, there may also be a more subtle influence of ongoing seizure activity. In the LH group, a longer duration of epilepsy was associated with increasing atypical language lateralization (as previously shown in a small pediatric sample ²² ). This may differ in nature from the more extensive reorganization associated with early LH injury, and instead reflect increasing functional adaptation or compensation from the RH. This is akin to the influence of healthy aging on increasing bilateral language representation ¹⁴ , ³¹ (see the HAROLD model, Hemispheric Asymmetry Reduction in Older Adults ³⁴ ).

Future research should examine whether such increasing bilaterality with age is seen in epilepsy and disentangle the contribution of healthy aging and chronic seizures on changes in language lateralization with age. Examination of not only the difference in activation between the two hemispheres, but the changes in absolute activation in each hemisphere, as has been done in development, ³ may help us to distinguish between reorganization and compensation mechanisms. In addition, the use of functional connectivity measures may also disentangle reorganization and compensation, both during development and aging. A functional connectivity measure has been developed that compares inter‐ and intrahemispheric connectivity of language regions during resting‐state fMRI. ³⁵ , ³⁶ This measure could have consequences for understanding the efficiency of reorganization and providing additional information for preoperative evaluation.

4.3. Handedness

Left and ambidextrous handedness was a predictor of greater atypical language lateralization across both LH and RH groups. This was contrary to a previous study showing that the relationship between handedness and language lateralization was specific to those with a LH epilepsy focus (in an adult temporal lobe epilepsy sample). ²³ In addition, left and ambidextrous handedness also predicted atypical language lateralization in the temporal lobe, although this was only significant in the LH epilepsy group. The presence of the association between atypical language lateralization and handedness in both the LH and RH groups, at least in the frontal lobe, may partially reflect the higher rates of atypical language lateralization in left‐handed individual in the general population. ³¹ , ³² However, there may also be an added effect of epilepsy on handedness ⁶ , ¹³ and the relationship between handedness and language lateralization has been shown to be stronger in individuals with LH epilepsy than in controls. ³³

Consistent with this, we demonstrated that left/ambidextrous handedness was associated with frontal involvement in the LH but not the RH epilepsy groups (see Data S1). It is possible that this reflects either joint reorganization of language and handedness in response to a left frontal lobe pathology, or a facilitative role of reorganization of one on the other. Overall, the role of handedness as a predictor of language lateralization may reflect both genetic and epilepsy‐associated effects in the LH group, but predominantly the former in the RH group. Information on family sinistrality in future studies would help to disentangle the contributions of these two factors.

4.4. Atypical language lateralization in individuals with RH epilepsy

In the RH group, we were unable to identify predictors of language lateralization, beyond left/ambidextrous handedness. This may be due in part to the smaller sample size and greater between‐sample variance (random‐effects) compared to the LH sample. However, atypical language lateralization was still higher in the RH epilepsy group than we would expect in the general population (20% in right handers, 46% of left handers). Figure 1 shows a cluster of patients with RH epilepsy with atypical language lateralization and an onset of epilepsy in childhood. An earlier age at seizure onset was a borderline predictor of atypical language lateralization in this group (p = .081). This may reflect the putative role of the right hemisphere in language development in early childhood. ³ In addition, atypical language lateralization was demonstrated in two of the three RH stroke patients included in our sample (see Figure 2). Both of these patients remained right‐handed, suggesting that they did not have preexisting atypical language lateralisation associated with left‐handedness. The potential causes of atypical language lateralization in individuals with RH epilepsy remain uncertain.

Notably, there was no difference in rates of atypical language lateralization between LH and RH epilepsy groups with no predictors (19% and 20%, respectively). This may indicate that at least some of the effect of seizures on language lateralization is of a bilateral nature. Given that there is often a contralateral spread of seizure activity, this could contribute toward the general increase in atypical language lateralization rates in individuals with epilepsy. Atypical language lateralization has been linked to the spread of seizure activity ipsilaterally in the LH ³⁷ but not to the RH. A small case series of LH patients showed no association between contralateral spread of seizure activity to the RH and atypical language lateralization. ⁷ However, further examination of this question in future research is needed and may help to elucidate the higher rates of atypical language lateralization in individuals with RH epilepsy compared to the general population.

4.5. Cumulative influence of individual predictors

Our analyses suggested that there was a cumulative effect of predictors on language lateralization, whereby having a greater number of predictors was associated with increasing atypical language lateralization. Given that suspected atypical language lateralization is one of the reasons patients are recommended for presurgical fMRI, ²⁸ better identification of predictors of atypical language lateralization should improve patient selection protocols. In the LH group, the number of clinical predictors may serve as a good indicator of language lateralization at an individual level, with a greater number of predictors leading to increased confidence that the patient may be atypically lateralized. This cumulative effect may be due to the interaction between such predictors. For example, early LH acquired insults in isolation are associated with reorganization, but this association appears to be strengthened in cases where the insult involves the frontal lobe, and perhaps even more so if it is also accompanied by the reorganization of handedness functions.

4.6. Limitations

There was a high proportion of unexplained variance in our models. It is likely that the heterogeneity in task methodology between samples also contributed to the unexplained variance in our final models, as language tasks can be lateralizing to a different degree, and this interacts with the ROI used. ³¹ This sample primarily included laterality indices calculated using a frontal ROI (89%); therefore, our findings likely reflect patterns and predictors of frontal language lateralization only. Given higher rates of crossed dominance in individuals with epilepsy, ¹ predictors of atypical language lateralization may vary based on whether frontal or temporal ROI were used for LI calculation. Indeed, only left/ambidextrous handedness and a history of stroke were also significant predictors of atypical temporal lobe language lateralization in the LH epilepsy group. In addition, there were no predictors of temporal language lateralization in the RH epilepsy group, and our overall models explained less variance in LI than the models predicting predominantly frontal language lateralization. This is despite atypical temporal language lateralization being more common in our sample.

5. CONCLUSION

Overall, our findings were largely consistent with theories of language plasticity proposing greater reorganization after early LH insult. Early LH acquired injuries were robust predictors of atypical language lateralization, particularly when combined with a frontal lobe location and atypical handedness. Other mechanisms beyond early plasticity may underlie atypical language lateralization in the wider sample, including increasing bilaterality with a longer duration of epilepsy. This suggests the presence of different mechanisms underlying atypical language lateralization in epilepsy: one associated with early developmental plasticity and another with the effect of chronic seizures. These findings predominantly reflect patterns of frontal lobe language lateralization, with only some replicated in the temporal lobe. Our cumulative predictor model provides a practical way to identify those who are more likely to demonstrate atypical language lateralization in the frontal lobe. However, high rates of atypical language lateralization in RH epilepsy sample suggests that presurgical fMRI should be considered for all surgical candidates when surgery would involve language or memory critical cortex.

AUTHOR CONTRIBUTIONS

F.P., L.C., J.M., F.L., and T.B. contributed to the conception and design of this study. F.P., M.H.E., J.M., L.N.S., M.M.B., W.D.G., and T.B. contributed to the acquisition and analysis of data. F.P., M.H.E., F.L., and T.B. contributed to drafting a significant portion of the manuscript or figures.

CONFLICT OF INTEREST STATEMENT

The authors have no conflicts of interest to declare. We confirm that we have read the Journal's position on issues involved in ethical publication and affirm that this report is consistent with those guidelines.

Supporting information

Data S1.

EPI-66-2842-s001.docx^{(31.5KB, docx)}

ACKNOWLEDGMENTS

We are ever so grateful to the authors who responded to our request for data, whether those data were available or not. This work was supported by the National Institute for Health and Care Research Great Ormond Street Hospital Biomedical Research Centre). Freya Prentice is supported by the Child Health Research Studentship, funded by the Child Health Research Charitable Incorporated Organization and spent 8 weeks at the Children's National Hospital in Washington, DC, funded by The Charlotte and Yule Bogue Research Fellowships in Honor of Sir Charles Lovatt Evans and A.J. Clark. Maria H. Eriksson is supported by the Child Health Research Studentship, funded by the National Institute for Health and Care Research Great Ormond Street Hospital Biomedical Research Centre and the Sigrid Jusélius Foundation. Leigh N. Sepeta is supported by a K23 grant (K23 NINDS NS093152).

Prentice F, Chehabeddine L, Eriksson MH, Murphy J, Sepeta LN, Gaillard WD, et al. Predictors of atypical language lateralization in focal epilepsy: A mega‐analysis of fMRI evidence. Epilepsia. 2025;66:2842–2852. 10.1111/epi.18422

DATA AVAILABILITY STATEMENT

The data that support the findings of this study are available from the corresponding author upon reasonable request. For the small proportion of these data shared by the original study authors, requests will be forwarded onto the author of the original study.

REFERENCES

1. Berl MM, Zimmaro LA, Khan OI, Dustin I, Ritzl E, Duke ES, et al. Characterization of atypical language activation patterns in focal epilepsy. Ann Neurol. 2014;75(1):33–42. 10.1002/ana.24015 [DOI] [PMC free article] [PubMed] [Google Scholar]
2. Berl MM, Mayo J, Parks EN, Rosenberger LR, VanMeter J, Ratner NB, et al. Regional differences in the developmental trajectory of lateralization of the language network. Hum Brain Mapp. 2014;35(1):270–284. 10.1002/hbm.22179 [DOI] [PMC free article] [PubMed] [Google Scholar]
3. Olulade OA, Seydell‐Greenwald A, Chambers CE, Turkeltaub PE, Dromerick AW, Berl MM, et al. The neural basis of language development: changes in lateralization over age. Proc Natl Acad Sci USA. 2020;117(38):23477–23483. 10.1073/pnas.1905590117 [DOI] [PMC free article] [PubMed] [Google Scholar]
4. Basser LS. Hemiplegia of early onset and the faculty of speech with special reference to the effects of hemispherectomy. Brain. 1962;85:427–460. 10.1093/brain/85.3.427 [DOI] [PubMed] [Google Scholar]
5. Lenneberg E. Biological foundations of language. Hoboken, NJ: John Wiley; 1967. [Google Scholar]
6. Rasmussen T, Milner B. The role of early left‐brain injury in determining lateralization of cerebral speech functions. Ann N Y Acad Sci. 1977;299:355–369. 10.1111/j.1749-6632.1977.tb41921.x [DOI] [PubMed] [Google Scholar]
7. Liegeois F, Connelly A, Cross JH, Boyd SG, Gadian DG, Vargha‐Khadem F, et al. Language reorganization in children with early‐onset lesions of the left hemisphere: an fMRI study. Brain. 2004;127(Pt 6):1229–1236. 10.1093/brain/awh159 [DOI] [PubMed] [Google Scholar]
8. Berl MM, Balsamo LM, Xu B, Moore EN, Weinstein SL, Conry JA, et al. Seizure focus affects regional language networks assessed by fMRI. Neurology. 2005;65(10):1604–1611. 10.1212/01.wnl.0000184502.06647.28 [DOI] [PubMed] [Google Scholar]
9. Janszky J, Mertens M, Janszky I, Ebner A, Woermann FG. Left‐sided interictal epileptic activity induces shift of language lateralization in temporal lobe epilepsy: an fMRI study. Epilepsia. 2006;47(5):921–927. 10.1111/j.1528-1167.2006.00514.x [DOI] [PubMed] [Google Scholar]
10. Brázdil M, Zákopcan J, Kuba R, Fanfrdlová Z, Rektor I. Atypical hemispheric language dominance in left temporal lobe epilepsy as a result of the reorganization of language functions. Epilepsy Behav. 2003;4(4):414–419. 10.1016/s1525-5050(03)00119-7 [DOI] [PubMed] [Google Scholar]
11. Adcock JE, Wise RG, Oxbury JM, Oxbury SM, Matthews PM. Quantitative fMRI assessment of the differences in lateralization of language‐related brain activation in patients with temporal lobe epilepsy. NeuroImage. 2003;18(2):423–438. 10.1016/s1053-8119(02)00013-7 [DOI] [PubMed] [Google Scholar]
12. Carpentier A, Pugh KR, Westerveld M, Studholme C, Skrinjar O, Thompson JL, et al. Functional MRI of language processing: dependence on input modality and temporal lobe epilepsy. Epilepsia. 2001;42(10):1241–1254. [DOI] [PubMed] [Google Scholar]
13. Helmstaedter C, Kurthen M, Linke DB, Elger CE. Patterns of language dominance in focal left and right hemisphere epilepsies: relation to MRI findings, EEG, sex, and age at onset of epilepsy. Brain Cogn. 1997;33(2):135–150. 10.1006/brcg.1997.0888 [DOI] [PubMed] [Google Scholar]
14. Springer JA, Binder JR, Hammeke TA, Swanson SJ, Frost JA, Bellgowan PS, et al. Language dominance in neurologically normal and epilepsy subjects: a functional MRI study. Brain. 1999;122(Pt 11):2033–2046. 10.1093/brain/122.11.2033 [DOI] [PubMed] [Google Scholar]
15. Woermann FG, Jokeit H, Luerding R, Freitag H, Schulz R, Guertler S, et al. Language lateralization by Wada test and fMRI in 100 patients with epilepsy. Neurology. 2003;61(5):699–701. 10.1212/01.wnl.0000078815.03224.57 [DOI] [PubMed] [Google Scholar]
16. Satz P, Strauss E, Whitaker H. The ontogeny of hemispheric specialization: some old hypotheses revisited. Brain Lang. 1990;38(4):596–614. 10.1016/0093-934x(90)90139-8 [DOI] [PubMed] [Google Scholar]
17. Vargha‐Khadem F, Isaacs E, Watkins K, Mishkin M. Ontogenetic specialisation of hemispheric function. In: Oxbury JM, Polkey CE, Duchowny MS, editors. Intractable focal epilepsy. Philadelphia, PA: W. B. Saunders; 2000. [Google Scholar]
18. Prentice F, Chehabeddine L, Eriksson MH, Murphy J, Sepeta LN, Gaillard WD, et al. Is an earlier onset of focal epilepsy associated with atypical language lateralization? A systematic review, meta‐analysis and new data. Neuroscience & Biobehavioral Reviews. 2025;172:106110. 10.1016/j.neubiorev.2025.106110 [DOI] [PubMed] [Google Scholar]
19. Duchowny M, Jayakar P, Harvey AS, Resnick T, Alvarez L, Dean P, et al. Language cortex representation: effects of developmental versus acquired pathology. Ann Neurol. 1996;40(1):31–38. 10.1002/ana.410400108 [DOI] [PubMed] [Google Scholar]
20. Gaillard WD, Berl MM, Moore EN, Ritzl EK, Rosenberger LR, Weinstein SL, et al. Atypical language in lesional and nonlesional complex partial epilepsy. Neurology. 2007;69(18):1761–1771. 10.1212/01.wnl.0000289650.48830.1a [DOI] [PubMed] [Google Scholar]
21. Rathore C, George A, Kesavadas C, Sarma PS, Radhakrishnan K. Extent of initial injury determines language lateralization in mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE‐HS). Epilepsia. 2009;50(10):2249–2255. 10.1111/j.1528-1167.2009.02300.x [DOI] [PubMed] [Google Scholar]
22. Marcelle M, You X, Fanto EJ, Sepeta LN, Gaillard WD, Berl MM. Impact of development and recent‐onset epilepsy on language dominance. Epilepsia. 2022;63(10):2637–2649. 10.1111/epi.17383 [DOI] [PMC free article] [PubMed] [Google Scholar]
23. Stewart CC, Swanson SJ, Sabsevitz DS, Rozman ME, Janecek JK, Binder JR. Predictors of language lateralization in temporal lobe epilepsy. Neuropsychologia. 2014;60:93–102. 10.1016/j.neuropsychologia.2014.05.021 [DOI] [PMC free article] [PubMed] [Google Scholar]
24. Duke ES, Tesfaye M, Berl MM, Walker JE, Ritzl EK, Fasano RE, et al. The effect of seizure focus on regional language processing areas. Epilepsia. 2012;53(6):1044–1050. 10.1111/j.1528-1167.2012.03490.x [DOI] [PMC free article] [PubMed] [Google Scholar]
25. Weber B, Wellmer J, Reuber M, Mormann F, Weis S, Urbach H, et al. Left hippocampal pathology is associated with atypical language lateralization in patients with focal epilepsy. Brain. 2006;129(Pt 2):346–351. 10.1093/brain/awh694 [DOI] [PubMed] [Google Scholar]
26. Pahs G, Rankin P, Helen Cross J, Croft L, Northam GB, Liegeois F, et al. Asymmetry of planum temporale constrains interhemispheric language plasticity in children with focal epilepsy. Brain. 2013;136(Pt 10):3163–3175. 10.1093/brain/awt225 [DOI] [PMC free article] [PubMed] [Google Scholar]
27. Oh YM, Koh EJ. Language lateralization in patients with temporal lobe epilepsy: a comparison between volumetric analysis and the Wada test. J Korean Neurosurg Soc. 2009;45(6):329–335. 10.3340/jkns.2009.45.6.329 [DOI] [PMC free article] [PubMed] [Google Scholar]
28. Vogt VL, Äikiä M, Del Barrio A, Boon P, Borbély C, Bran E, et al. Current standards of neuropsychological assessment in epilepsy surgery centers across Europe. Epilepsia. 2017;58(3):343–355. 10.1111/epi.13646 [DOI] [PubMed] [Google Scholar]
29. Harrington GS, Buonocore MH, Farias ST. Intrasubject reproducibility of functional MR imaging activation in language tasks. AJNR Am J Neuroradiol. 2006;27(4):938–944. [PMC free article] [PubMed] [Google Scholar]
30. Bradshaw AR, Thompson PA, Wilson AC, Bishop DVM, Woodhead ZVJ. Measuring language lateralisation with different language tasks: a systematic review. PeerJ. 2017;5:e3929. 10.7717/peerj.3929 [DOI] [PMC free article] [PubMed] [Google Scholar]
31. Szaflarski JP, Binder JR, Possing ET, McKiernan KA, Ward BD, Hammeke TA. Language lateralization in left‐handed and ambidextrous people: fMRI data. Neurology. 2002;59(2):238–244. 10.1212/wnl.59.2.238 [DOI] [PubMed] [Google Scholar]
32. Knecht S, Dräger B, Deppe M. Handedness and hemispheric language dominance in healthy humans. Brain. 2000;123(12):2512–2518. 10.1093/brain/123.12.2512 [DOI] [PubMed] [Google Scholar]
33. Slezicki KI, Cho YW, Yi SD, Brock MS, Pfeiffer MH, McVearry KM, et al. Incidence of atypical handedness in epilepsy and its association with clinical factors. Epilepsy Behav. 2009;16(2):330–334. 10.1016/j.yebeh.2009.08.006 [DOI] [PubMed] [Google Scholar]
34. Cabeza R. Hemispheric asymmetry reduction in older adults: the HAROLD model. Psychol Aging. 2002;17(1):85–100. 10.1037//0882-7974.17.1.85 [DOI] [PubMed] [Google Scholar]
35. Mbwana JS, You X, Ailion A, Fanto EJ, Krishnamurthy M, Sepeta LN, et al. Functional connectivity hemispheric contrast (FC‐HC): a new metric for language mapping. Neuroimage Clin. 2021;30:102598. 10.1016/j.nicl.2021.102598 [DOI] [PMC free article] [PubMed] [Google Scholar]
36. Ailion AS, You X, Mbwana JS, Fanto EJ, Krishnamurthy M, Vaidya CJ, et al. Functional connectivity as a potential mechanism for language plasticity. Neurology. 2022;98(3):e249–e259. 10.1212/WNL.0000000000013071 [DOI] [PMC free article] [PubMed] [Google Scholar]
37. Janszky J, Ebner A, Kruse B, Mertens M, Jokeit H, Seitz RJ, et al. Functional organization of the brain with malformations of cortical development. Ann Neurol. 2003;53(6):759–767. [DOI] [PubMed] [Google Scholar]

Associated Data

This section collects any data citations, data availability statements, or supplementary materials included in this article.

Supplementary Materials

Data S1.

EPI-66-2842-s001.docx^{(31.5KB, docx)}

Data Availability Statement

[epi18422-bib-0001] 1. Berl MM, Zimmaro LA, Khan OI, Dustin I, Ritzl E, Duke ES, et al. Characterization of atypical language activation patterns in focal epilepsy. Ann Neurol. 2014;75(1):33–42. 10.1002/ana.24015 [DOI] [PMC free article] [PubMed] [Google Scholar]

[epi18422-bib-0002] 2. Berl MM, Mayo J, Parks EN, Rosenberger LR, VanMeter J, Ratner NB, et al. Regional differences in the developmental trajectory of lateralization of the language network. Hum Brain Mapp. 2014;35(1):270–284. 10.1002/hbm.22179 [DOI] [PMC free article] [PubMed] [Google Scholar]

[epi18422-bib-0003] 3. Olulade OA, Seydell‐Greenwald A, Chambers CE, Turkeltaub PE, Dromerick AW, Berl MM, et al. The neural basis of language development: changes in lateralization over age. Proc Natl Acad Sci USA. 2020;117(38):23477–23483. 10.1073/pnas.1905590117 [DOI] [PMC free article] [PubMed] [Google Scholar]

[epi18422-bib-0004] 4. Basser LS. Hemiplegia of early onset and the faculty of speech with special reference to the effects of hemispherectomy. Brain. 1962;85:427–460. 10.1093/brain/85.3.427 [DOI] [PubMed] [Google Scholar]

[epi18422-bib-0005] 5. Lenneberg E. Biological foundations of language. Hoboken, NJ: John Wiley; 1967. [Google Scholar]

[epi18422-bib-0006] 6. Rasmussen T, Milner B. The role of early left‐brain injury in determining lateralization of cerebral speech functions. Ann N Y Acad Sci. 1977;299:355–369. 10.1111/j.1749-6632.1977.tb41921.x [DOI] [PubMed] [Google Scholar]

[epi18422-bib-0007] 7. Liegeois F, Connelly A, Cross JH, Boyd SG, Gadian DG, Vargha‐Khadem F, et al. Language reorganization in children with early‐onset lesions of the left hemisphere: an fMRI study. Brain. 2004;127(Pt 6):1229–1236. 10.1093/brain/awh159 [DOI] [PubMed] [Google Scholar]

[epi18422-bib-0008] 8. Berl MM, Balsamo LM, Xu B, Moore EN, Weinstein SL, Conry JA, et al. Seizure focus affects regional language networks assessed by fMRI. Neurology. 2005;65(10):1604–1611. 10.1212/01.wnl.0000184502.06647.28 [DOI] [PubMed] [Google Scholar]

[epi18422-bib-0009] 9. Janszky J, Mertens M, Janszky I, Ebner A, Woermann FG. Left‐sided interictal epileptic activity induces shift of language lateralization in temporal lobe epilepsy: an fMRI study. Epilepsia. 2006;47(5):921–927. 10.1111/j.1528-1167.2006.00514.x [DOI] [PubMed] [Google Scholar]

[epi18422-bib-0010] 10. Brázdil M, Zákopcan J, Kuba R, Fanfrdlová Z, Rektor I. Atypical hemispheric language dominance in left temporal lobe epilepsy as a result of the reorganization of language functions. Epilepsy Behav. 2003;4(4):414–419. 10.1016/s1525-5050(03)00119-7 [DOI] [PubMed] [Google Scholar]

[epi18422-bib-0011] 11. Adcock JE, Wise RG, Oxbury JM, Oxbury SM, Matthews PM. Quantitative fMRI assessment of the differences in lateralization of language‐related brain activation in patients with temporal lobe epilepsy. NeuroImage. 2003;18(2):423–438. 10.1016/s1053-8119(02)00013-7 [DOI] [PubMed] [Google Scholar]

[epi18422-bib-0012] 12. Carpentier A, Pugh KR, Westerveld M, Studholme C, Skrinjar O, Thompson JL, et al. Functional MRI of language processing: dependence on input modality and temporal lobe epilepsy. Epilepsia. 2001;42(10):1241–1254. [DOI] [PubMed] [Google Scholar]

[epi18422-bib-0013] 13. Helmstaedter C, Kurthen M, Linke DB, Elger CE. Patterns of language dominance in focal left and right hemisphere epilepsies: relation to MRI findings, EEG, sex, and age at onset of epilepsy. Brain Cogn. 1997;33(2):135–150. 10.1006/brcg.1997.0888 [DOI] [PubMed] [Google Scholar]

[epi18422-bib-0014] 14. Springer JA, Binder JR, Hammeke TA, Swanson SJ, Frost JA, Bellgowan PS, et al. Language dominance in neurologically normal and epilepsy subjects: a functional MRI study. Brain. 1999;122(Pt 11):2033–2046. 10.1093/brain/122.11.2033 [DOI] [PubMed] [Google Scholar]

[epi18422-bib-0015] 15. Woermann FG, Jokeit H, Luerding R, Freitag H, Schulz R, Guertler S, et al. Language lateralization by Wada test and fMRI in 100 patients with epilepsy. Neurology. 2003;61(5):699–701. 10.1212/01.wnl.0000078815.03224.57 [DOI] [PubMed] [Google Scholar]

[epi18422-bib-0016] 16. Satz P, Strauss E, Whitaker H. The ontogeny of hemispheric specialization: some old hypotheses revisited. Brain Lang. 1990;38(4):596–614. 10.1016/0093-934x(90)90139-8 [DOI] [PubMed] [Google Scholar]

[epi18422-bib-0017] 17. Vargha‐Khadem F, Isaacs E, Watkins K, Mishkin M. Ontogenetic specialisation of hemispheric function. In: Oxbury JM, Polkey CE, Duchowny MS, editors. Intractable focal epilepsy. Philadelphia, PA: W. B. Saunders; 2000. [Google Scholar]

[epi18422-bib-0018] 18. Prentice F, Chehabeddine L, Eriksson MH, Murphy J, Sepeta LN, Gaillard WD, et al. Is an earlier onset of focal epilepsy associated with atypical language lateralization? A systematic review, meta‐analysis and new data. Neuroscience & Biobehavioral Reviews. 2025;172:106110. 10.1016/j.neubiorev.2025.106110 [DOI] [PubMed] [Google Scholar]

[epi18422-bib-0019] 19. Duchowny M, Jayakar P, Harvey AS, Resnick T, Alvarez L, Dean P, et al. Language cortex representation: effects of developmental versus acquired pathology. Ann Neurol. 1996;40(1):31–38. 10.1002/ana.410400108 [DOI] [PubMed] [Google Scholar]

[epi18422-bib-0020] 20. Gaillard WD, Berl MM, Moore EN, Ritzl EK, Rosenberger LR, Weinstein SL, et al. Atypical language in lesional and nonlesional complex partial epilepsy. Neurology. 2007;69(18):1761–1771. 10.1212/01.wnl.0000289650.48830.1a [DOI] [PubMed] [Google Scholar]

[epi18422-bib-0021] 21. Rathore C, George A, Kesavadas C, Sarma PS, Radhakrishnan K. Extent of initial injury determines language lateralization in mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE‐HS). Epilepsia. 2009;50(10):2249–2255. 10.1111/j.1528-1167.2009.02300.x [DOI] [PubMed] [Google Scholar]

[epi18422-bib-0022] 22. Marcelle M, You X, Fanto EJ, Sepeta LN, Gaillard WD, Berl MM. Impact of development and recent‐onset epilepsy on language dominance. Epilepsia. 2022;63(10):2637–2649. 10.1111/epi.17383 [DOI] [PMC free article] [PubMed] [Google Scholar]

[epi18422-bib-0023] 23. Stewart CC, Swanson SJ, Sabsevitz DS, Rozman ME, Janecek JK, Binder JR. Predictors of language lateralization in temporal lobe epilepsy. Neuropsychologia. 2014;60:93–102. 10.1016/j.neuropsychologia.2014.05.021 [DOI] [PMC free article] [PubMed] [Google Scholar]

[epi18422-bib-0024] 24. Duke ES, Tesfaye M, Berl MM, Walker JE, Ritzl EK, Fasano RE, et al. The effect of seizure focus on regional language processing areas. Epilepsia. 2012;53(6):1044–1050. 10.1111/j.1528-1167.2012.03490.x [DOI] [PMC free article] [PubMed] [Google Scholar]

[epi18422-bib-0025] 25. Weber B, Wellmer J, Reuber M, Mormann F, Weis S, Urbach H, et al. Left hippocampal pathology is associated with atypical language lateralization in patients with focal epilepsy. Brain. 2006;129(Pt 2):346–351. 10.1093/brain/awh694 [DOI] [PubMed] [Google Scholar]

[epi18422-bib-0026] 26. Pahs G, Rankin P, Helen Cross J, Croft L, Northam GB, Liegeois F, et al. Asymmetry of planum temporale constrains interhemispheric language plasticity in children with focal epilepsy. Brain. 2013;136(Pt 10):3163–3175. 10.1093/brain/awt225 [DOI] [PMC free article] [PubMed] [Google Scholar]

[epi18422-bib-0027] 27. Oh YM, Koh EJ. Language lateralization in patients with temporal lobe epilepsy: a comparison between volumetric analysis and the Wada test. J Korean Neurosurg Soc. 2009;45(6):329–335. 10.3340/jkns.2009.45.6.329 [DOI] [PMC free article] [PubMed] [Google Scholar]

[epi18422-bib-0028] 28. Vogt VL, Äikiä M, Del Barrio A, Boon P, Borbély C, Bran E, et al. Current standards of neuropsychological assessment in epilepsy surgery centers across Europe. Epilepsia. 2017;58(3):343–355. 10.1111/epi.13646 [DOI] [PubMed] [Google Scholar]

[epi18422-bib-0029] 29. Harrington GS, Buonocore MH, Farias ST. Intrasubject reproducibility of functional MR imaging activation in language tasks. AJNR Am J Neuroradiol. 2006;27(4):938–944. [PMC free article] [PubMed] [Google Scholar]

[epi18422-bib-0030] 30. Bradshaw AR, Thompson PA, Wilson AC, Bishop DVM, Woodhead ZVJ. Measuring language lateralisation with different language tasks: a systematic review. PeerJ. 2017;5:e3929. 10.7717/peerj.3929 [DOI] [PMC free article] [PubMed] [Google Scholar]

[epi18422-bib-0031] 31. Szaflarski JP, Binder JR, Possing ET, McKiernan KA, Ward BD, Hammeke TA. Language lateralization in left‐handed and ambidextrous people: fMRI data. Neurology. 2002;59(2):238–244. 10.1212/wnl.59.2.238 [DOI] [PubMed] [Google Scholar]

[epi18422-bib-0032] 32. Knecht S, Dräger B, Deppe M. Handedness and hemispheric language dominance in healthy humans. Brain. 2000;123(12):2512–2518. 10.1093/brain/123.12.2512 [DOI] [PubMed] [Google Scholar]

[epi18422-bib-0033] 33. Slezicki KI, Cho YW, Yi SD, Brock MS, Pfeiffer MH, McVearry KM, et al. Incidence of atypical handedness in epilepsy and its association with clinical factors. Epilepsy Behav. 2009;16(2):330–334. 10.1016/j.yebeh.2009.08.006 [DOI] [PubMed] [Google Scholar]

[epi18422-bib-0034] 34. Cabeza R. Hemispheric asymmetry reduction in older adults: the HAROLD model. Psychol Aging. 2002;17(1):85–100. 10.1037//0882-7974.17.1.85 [DOI] [PubMed] [Google Scholar]

[epi18422-bib-0035] 35. Mbwana JS, You X, Ailion A, Fanto EJ, Krishnamurthy M, Sepeta LN, et al. Functional connectivity hemispheric contrast (FC‐HC): a new metric for language mapping. Neuroimage Clin. 2021;30:102598. 10.1016/j.nicl.2021.102598 [DOI] [PMC free article] [PubMed] [Google Scholar]

[epi18422-bib-0036] 36. Ailion AS, You X, Mbwana JS, Fanto EJ, Krishnamurthy M, Vaidya CJ, et al. Functional connectivity as a potential mechanism for language plasticity. Neurology. 2022;98(3):e249–e259. 10.1212/WNL.0000000000013071 [DOI] [PMC free article] [PubMed] [Google Scholar]

[epi18422-bib-0037] 37. Janszky J, Ebner A, Kruse B, Mertens M, Jokeit H, Seitz RJ, et al. Functional organization of the brain with malformations of cortical development. Ann Neurol. 2003;53(6):759–767. [DOI] [PubMed] [Google Scholar]

PERMALINK

Predictors of atypical language lateralization in focal epilepsy: A mega‐analysis of fMRI evidence

Freya Prentice

Lara Chehabeddine

Maria Helena Eriksson

Jennifer Murphy

Leigh N Sepeta

William D Gaillard

Madison M Berl

Frédérique Liégeois

Torsten Baldeweg

Abstract

Objective

Methods

Results

Significance

Key points.

1. INTRODUCTION

2. MATERIALS AND METHODS

2.1. Mega‐analysis dataset

2.2. Measures

2.2.1. Laterality indices

2.2.2. Predictor variables

2.3. Analysis strategy

2.3.1. Identification of predictors of language lateralization

2.3.2. Calculation of a “predictor score” for language lateralization

2.3.3. Identification of predictors of left/ambidextrous handedness

3. RESULTS

3.1. Sample characteristics

TABLE 1.

3.2. Side of epilepsy

3.3. Identification of predictors of language lateralization

TABLE 2.

FIGURE 1.

3.4. Interactions with side of epilepsy

FIGURE 2.

3.5. Cumulative influence of predictor variables on language lateralization

FIGURE 3.

4. DISCUSSION

4.1. Acquired insults drive language reorganization

4.2. Chronicity effect of seizures on language lateralization

4.3. Handedness

4.4. Atypical language lateralization in individuals with RH epilepsy

4.5. Cumulative influence of individual predictors

4.6. Limitations

5. CONCLUSION

AUTHOR CONTRIBUTIONS

CONFLICT OF INTEREST STATEMENT

Supporting information

ACKNOWLEDGMENTS

DATA AVAILABILITY STATEMENT

REFERENCES

Associated Data

Supplementary Materials

Data Availability Statement

ACTIONS

PERMALINK

RESOURCES

Similar articles

Cited by other articles

Links to NCBI Databases