Noninvasive Assessment of Language Laterality in Pre-Surgical Epilepsy Patients
An estimated 15% of all patients with focal epilepsy syndromes do not experience substantial relief when treated with anticonvulsant medications alone . For these patients with intractable epilepsy, surgical intervention is often indicated . In order to maximize postoperative benefits and minimize the risk of associated impairments, such patients undergo presurgical epilepsy evaluations prior to treatment . Evaluations are conducted by a multidisciplinary team and typically include reports of clinical semiology (signs and symptoms of the seizure activity), structural and functional neuroimaging, electroencephalography (EEG) video telemetry, and neuropsychological testing. Primary goals of the presurgical evaluation are to map the epileptogenic area (a conceptual area of the cortex, believed to be indispensable in the generation of seizure activity; [1, 4]) and eloquent cortex (critical language, sensorimotor, and memory areas which are avoided as much as possible during surgery) to guide surgical procedures and predict postsurgical functioning. With regard to language, the primary objective is to identify the dominant hemisphere involved in language functions (i.e. language laterality ), although noninvasive imaging modalities have made it possible to map discrete language functions with improved spatial and temporal detail.
The intracarotid amobarbital procedure (Wada test; ) remains the current gold-standard in a clinical evaluation of language laterality. However, the procedure can include medical complications in up to 3% of cases and provides relatively crude hemispheric data . Limitations of the Wada test have led to developments in non-invasive neuroimaging modalities [8, 9], primarily functional Magnetic Resonance Imaging (fMRI) and magnetoencephalography (MEG). fMRI measures blood oxygenation levels as a proxy for brain activity in response to cognitive tasks. An alternative method known as resting state fMRI, tracks blood oxygenation levels in the absence of an explicit task as a proxy for large-scale brain activity . Alternatively, MEG measures electromagnetic fluctuations outside the skull as a proxy for brain activity and this method has higher spatial and temporal sensitivity compared to fMRI. The most common MEG analysis used in language laterality is dipole fitting, which fits single or multiple dipoles within the brain and indicates their corresponding strength and orientation . An advanced method of signal processing and source localization in MEG, called beamforming, has recently allowed for meaningful data to be extracted from patients with metal implants (e.g. shunts, braces, and vagus nerve stimulators) which normally cause artifacts that render neuroimaging data uninterpretable .
Noninvasive imaging tools are used with a wide variety of language tasks and analytic methods, therefore they have contributed substantially to language mapping in presurgical epilepsy cases. Laterality indices can be quantified and classified by adjusting a multitude of parameters including p-values at a voxel level, threshold levels, baseline and active windows, etc. . Language laterality has been assessed across numerous tasks, including a variety of verbal fluency tasks (e.g. phonemic fluency, verb generation), passive speech listening, text reading, phonemic judgment, semantic decision, sentence comprehension, and naming . Although the strength and pattern of lateralization varies across tasks and is thought to represent true variability in language networks, laterality indices are strongest in verbal fluency tasks . For instance, verb generation and phonemic fluency tasks produce strong laterality indices in frontal regions [13, 14, 15], and semantic fluency tasks produce strong laterality indices in temporoparietal regions .
There are numerous challenges and potential gains associated with the implementation of fMRI, MEG, and other noninvasive imaging modalities in presurgical evaluations. Challenges primarily include the lack of normative data against which patients can be compared (especially in pediatrics ) and insufficient guidelines to direct task selection, analysis, and interpretation [3, 5]. For these reasons, the Wada test remains the current gold-standard in clinical practice, although many epilepsy centers have integrated fMRI and MEG into presurgical evaluations to further validate or expand upon neuropsychological findings .
A particularly promising application for noninvasive imaging is the development of passive language tasks. Noncompliant and pediatric patients experience difficulty with standard task demands, such as verbal fluency paradigms. However, passive tasks (e.g. listening to a story) require minimal attentional and linguistic demands, therefore they may yield valid laterality indices in patients who otherwise would be considered untestable due to clinical complications or developmental limitations .
Title: Language lateralization of a bilingual person with epilepsy using a combination of
fMRI and neuropsychological assessment findings
Citation: O’Grady, C., Omisade, A., & Sadler, R. M. (2016). Language lateralization of a bilingual person with epilepsy using a combination of fMRI and neuropsychological assessment findings. Neurocase, 22(5), 436-442.
Abstract: This report describes the findings of language functional magnetic resonance imaging (fMRI) in a left-handed Urdu and English speaker with right hemisphere-originating epilepsy and unclear language dominance. fMRI is a reliable method for determining hemispheric language dominance in presurgical planning. However, the effects of bilingualism on language activation depend on many factors including age of acquisition and proficiency in the tested language, and morphological properties of the language itself. This case demonstrates that completing fMRI in both spoken languages and interpreting the results within the context of a neuropsychological assessment are essential in arriving at accurate conclusions about language distribution in bilingual patients.
1. Engel, J. (1993). Update on surgical treatment of the epilepsies Summary of The Second International Palm Desert Conference on the Surgical Treatment of the Epilepsies (1992). Neurology, 43(8), 1612-1612.
2. Rosenow, F., & Lüders, H. (2001). Presurgical evaluation of epilepsy. Brain, 124(9), 1683-1700.
3. Bradshaw, A. R., Bishop, D. V., & Woodhead, Z. V. (2017). Methodological considerations in assessment of language lateralisation with fMRI: a systematic review. PeerJ, 5, e3557.
4. Jehi, L. (2018). The Epileptogenic Zone: Concept and Definition. Epilepsy Currents, 18(1), 12-16.
5. Bradshaw, A. R., Thompson, P. A., Wilson, A. C., Bishop, D. V., & Woodhead, Z. V. (2017). Measuring language lateralisation with different language tasks: a systematic review. PeerJ, 5, e3929.
6. Wada, J., & Rasmussen, T. (1960). Intracarotid injection of sodium amytal for the lateralization of cerebral speech dominance: experimental and clinical observations. Journal of Neurosurgery, 17(2), 266-282.
7. Dion, J. E., Gates, P. C., Fox, A. J., Barnett, H. J., & Blom, R. J. (1987). Clinical events following neuroangiography: a prospective study. Stroke, 18(6), 997-1004.
8. Gaillard, W. D. (2000). Structural and functional imaging in children with partial epilepsy. Mental retardation and developmental disabilities research reviews, 6(3), 220-226.
9. Verrotti, A., Pizzella, V., Trotta, D., Madonna, L., Chiarelli, F., & Romani, G. L. (2003). Magnetoencephalography in pediatric neurology and in epileptic syndromes. Pediatric neurology, 28(4), 253-261.
10. Thomason, M. E., Dennis, E. L., Joshi, A. A., Joshi, S. H., Dinov, I. D., Chang, C., … & Glover, G. H. (2011). Resting-state fMRI can reliably map neural networks in children. Neuroimage, 55(1), 165-175.
11. Ebersole, J. S. (1997). Magnetoencephalography/magnetic source imaging in the assessment of patients with epilepsy.Epilepsia, 38(s4).
12. Stapleton-Kotloski, J. R., Kotloski, R. J., Boggs, J. A., Popli, G., O’Donovan, C. A., Couture, D. E., … & Godwin, D. W. (2014). Localization of interictal epileptiform activity using magnetoencephalography with synthetic aperture magnetometry in patients with a vagus nerve stimulator. Frontiers in neurology, 5, 244.
13. Kleinhans, N. M., Müller, R. A., Cohen, D. N., & Courchesne, E. (2008). Atypical functional lateralization of language in autism spectrum disorders. Brain research, 1221, 115-125.
14. Ruff, I. M., Brennan, N. P., Peck, K. K., Hou, B. L., Tabar, V., Brennan, C. W., & Holodny, A. I. (2008). Assessment of the language laterality index in patients with brain tumor using functional MR imaging: effects of thresholding, task selection, and prior surgery. American journal of neuroradiology, 29(3), 528-535.
15. Sanjuán, A., Bustamante, J. C., Forn, C., Ventura-Campos, N., Barrós-Loscertales, A., Martínez, J. C., … & Ávila, C. (2010). Comparison of two fMRI tasks for the evaluation of the expressive language function. Neuroradiology, 52(5), 407-415.
16. Jensen-Kondering, U. R., Ghobadi, Z., Wolff, S., Jansen, O., & Ulmer, S. (2012). Acoustically presented semantic decision-making tasks provide a robust depiction of the temporo-parietal speech areas. Journal of Clinical Neuroscience,19(3), 428-433.
17. Collinge, S., Prendergast, G., Mayers, S. T., Marshall, D., Siddell, P., Neilly, E., … & Zaman, A. (2017). Pre-surgical mapping of eloquent cortex for paediatric epilepsy surgery candidates: Evidence from a review of advanced functional neuroimaging. Seizure-European Journal of Epilepsy, 52, 136-146.
18. Arya, R., Wilson, J. A., Fujiwara, H., Vannest, J., Byars, A. W., Rozhkov, L., … & Horn, P. S. (2018). Electrocorticographic high‐gamma modulation with passive listening paradigm for pediatric extraoperative language mapping. Epilepsia, 59(4), 792-801.
Bradshaw, A. R., Thompson, P. A., Wilson, A. C., Bishop, D. V., & Woodhead, Z. V. (2017). Measuring language lateralisation with different language tasks: a systematic review. PeerJ, 5, e3929.
Collinge, S., Prendergast, G., Mayers, S. T., Marshall, D., Siddell, P., Neilly, E., … & Zaman, A. (2017). Pre-surgical mapping of eloquent cortex for paediatric epilepsy surgery candidates: Evidence from a review of advanced functional neuroimaging. Seizure-European Journal of Epilepsy, 52, 136-146.
Arya, R., Wilson, J. A., Fujiwara, H., Vannest, J., Byars, A. W., Rozhkov, L., … & Horn, P. S. (2018). Electrocorticographic high‐gamma modulation with passive listening paradigm for pediatric extraoperative language mapping. Epilepsia, 59(4), 792-801.
Additional Media and Resources
Guide to MEG by the Martinos Center at Massachusetts General Hospital: http://www.nmr.mgh.harvard.edu/meg/pdfs/talks/Cleve_Cohen_WithNotes2g.pdf
MATLAB Tutorial on Beamforming for MEG: http://www.fieldtriptoolbox.org/tutorial/natmeg/beamforming
Video of Wada Test by the Cleveland Clinic: https://youtu.be/N5_nX_LZ834
Video Description of the Epilepsy Presurgical Evaluation from the Epilepsy Foundation of America: https://youtu.be/UilImOfg7DM
Guidelines for using fMRI for presurgical evaluation of epilepsy: https://www.neurologyadvisor.com/epilepsy/epilepsy-surgery-evaluation-with-functional-mri-guidelines/article/632221/