Three- and four-dimensional mapping of speech and language in patients with epilepsy

Abstract

We have provided 3-D and 4D mapping of speech and language function based upon the results of direct cortical stimulation and event-related modulation of electrocorticography signals. Patients estimated to have right-hemispheric language dominance were excluded. Thus, 100 patients who underwent two-stage epilepsy surgery with chronic electrocorticography recording were studied. An older group consisted of 84 patients at least 10 years of age (7367 artefact-free non-epileptic electrodes), whereas a younger group included 16 children younger than age 10 (1438 electrodes). The probability of symptoms transiently induced by electrical stimulation was delineated on a 3D average surface image. The electrocorticography amplitude changes of high-gamma (70-110 Hz) and beta (15-30 Hz) activities during an auditory-naming task were animated on the average surface image in a 4D manner. Thereby, high-gamma augmentation and beta attenuation were treated as summary measures of cortical activation. Stimulation data indicated the causal relationship between (i) superior-temporal gyrus of either hemisphere and auditory hallucination; (ii) left superior-/middle-temporal gyri and receptive aphasia; (iii) widespread temporal/frontal lobe regions of the left hemisphere and expressive aphasia; and (iv) bilateral precentral/left posterior superior-frontal regions and speech arrest. On electrocorticography analysis, high-gamma augmentation involved the bilateral superior-temporal and precentral gyri immediately following question onset; at the same time, high-gamma activity was attenuated in the left orbitofrontal gyrus. High-gamma activity was augmented in the left temporal/frontal lobe regions, as well as left inferior-parietal and cingulate regions, maximally around question offset, with high-gamma augmentation in the left pars orbitalis inferior-frontal, middle-frontal, and inferior-parietal regions preceded by high-gamma attenuation in the contralateral homotopic regions. Immediately before verbal response, high-gamma augmentation involved the posterior superior-frontal and pre/postcentral regions, bilaterally. Beta-attenuation was spatially and temporally correlated with high-gamma augmentation in general but with exceptions. The younger and older groups shared similar spatial-temporal profiles of high-gamma and beta modulation; except, the younger group failed to show left-dominant activation in the rostral middle-frontal and pars orbitalis inferior-frontal regions around stimulus offset. The human brain may rapidly and alternately activate and deactivate cortical areas advantageous or obtrusive to function directed toward speech and language at a given moment. Increased left-dominant activation in the anterior frontal structures in the older age group may reflect developmental consolidation of the language system. The results of our functional mapping may be useful in predicting, across not only space but also time and patient age, sites specific to language function for presurgical evaluation of focal epilepsy.

Keywords: developmental consolidation; electrical stimulation; epilepsy surgery; high-frequency oscillations (HFOs); intracranial electrocorticography (ECoG) recording.

Figure 1

Regions of interest and distribution of subdural electrodes included in the analysis. (A) aCC = anterior cingulate gyrus; aFG = anterior fusiform gyrus; aITG = anterior inferior temporal gyrus; aMTG = anterior middle temporal gyrus; aSFG = anterior superior frontal gyrus; aSTG anterior superior temporal gyrus; cMFG = caudal middle frontal gyrus; Cun = cuneus gyrus; Ent = entorhinal gyrus; FP = frontal pole; IPL = inferior parietal lobule; iPoCG = inferior postcentral gyrus; iPreCG = inferior precentral gyrus; LG = lingual gyrus; LOG = lateral occipital gyrus; MOF = medial orbitofrontal gyrus; pCC = posterior cingulate gyrus; PCL = paracentral lobule; PCun = precuneus gyrus; pFG = posterior inferior temporal gyrus; PHG = parahippocampal gyrus; pITG = posterior inferior temporal gyrus; pMTG = posterior middle temporal gyrus; Pop/PTr/POr = pars opercularis/pars triangularis/pars orbitalis within the inferior frontal gyrus. LOF = lateral orbitofrontal gyrus; pSFG = posterior superior frontal gyrus; pSTG = posterior superior temporal gyrus; rMFG = rostral middle frontal gyrus; SMG = supramarginal gyrus; SPL = superior parietal lobule; sPoCG superior postcentral gyrus; sPreCG = superior precentral gyrus; TP = temporal pole. The numbers of ≥10-year-old (B) and (C) <10-year-old patients whose ECoG data at a given site contributed to further analysis are presented.

Figure 2

Task. Patients were asked to listen to a series of questions and to overtly verbalize a relevant answer during extraoperative ECoG recording. We then measured the per cent change of high-gamma amplitudes compared to the baseline period.

Figure 3

3D probabilistic mapping of cortical function based on the results of cortical stimulation in the older group. Auditory hallucination: perception of various pitches of sounds or alteration of the neuropsychologist’s voice’s pitch. Speech arrest: inability to initiate and continue vocalization not directly explained by the effect of forced jerking of tongue or lip. Expressive aphasia: dysnomia or inability to provide a relevant answer during a 5-s stimulation although the neuropsychologist (R.R.) confirmed that a given question was understood and the capability of vocalization was maintained. Receptive aphasia: inability to understand a question though being aware that a question was given by the neuropsychologist. To differentiate the nature of aphasia, the neuropsychologist asked each patient the reason, in case he/she failed to verbalize a relevant answer during stimulation. The locations of stimulation-induced sensory/motor symptoms are presented in Supplementary Fig. 2. The maps derived from the younger group are provided in Supplementary Fig. 3.

Figure 4

Snapshots of 4D mapping of speech and language based on the results of auditory naming-related modulation of high-gamma and beta activity in the older group. Event-related amplitude augmentation is reflected by red, whereas attenuation by blue. ‘+0.4’ indicates that the amplitude was augmented by 40% compared to the mean during the resting period between −600 and −200 ms relative to stimulus onset. (A) At +70 ms relative to stimulus onset, high-gamma and beta activities were both augmented in the superior-temporal gyri, bilaterally. (B) At +500 ms relative to stimulus onset, high-gamma activity was augmented, whereas beta activity was attenuated in the superior-temporal gyri, bilaterally. (C) At stimulus offset, widespread areas of the left temporal-frontal lobes as well as the right superior-temporal region showed high-gamma augmentation and beta attenuation. Simultaneously, widespread areas of the right frontal-parietal lobes showed high-gamma attenuation and beta augmentation. (D) Beta attenuation in widespread areas lingered between stimulus offset and response onset. Conversely, at response onset, high-gamma augmentation was confined to the posterior superior-frontal as well as pre-/postcentral gyri, bilaterally. Supplementary Videos 1 (older group) and 2 (younger group) delineate the spatiotemporal profiles of high-gamma and beta amplitude modulations in the lateral, medial, and inferior surfaces of the cerebral hemispheres relative to stimulus onset, stimulus offset, and response onset.

Figure 5

Region of interest analyses in the older group. (A) The changes of high-gamma (pink) and beta (blue) amplitudes within each region of interest are plotted relative to stimulus onset (bold line: mean; thin lines: standard error). Upper and lower horizontal bars indicate the timing when ECoG amplitudes were significantly augmented or attenuated compared to the baseline value during the resting period, respectively. ‘+0.2’ indicates 20% amplitude augmentation compared to the baseline value during the resting period. pSTG = posterior superior-temporal gyrus; iPreCG = inferior precentral gyrus; POr = pars orbitalis of the inferior-frontal gyrus. (B) The changes of ECoG amplitudes in the left hemisphere are plotted relative to stimulus offset. cMFG = caudal middle-frontal gyrus; ENT = entorhinal gyrus; IPL = inferior parietal lobule; pCC = posterior cingulate gyrus; PHG = parahippocampal gyrus; pMTG = posterior middle-temporal gyrus; pSFG = posterior superior-frontal gyrus; PTr = pars triangularis of the inferior-frontal gyrus. POp = pars opercularis of the inferior-frontal gyrus; rMFG = rostral middle-frontal gyrus; SMG = supramarginal gyrus. (C) The changes of ECoG amplitudes in the right hemisphere are plotted relative to stimulus offset. (D) The changes of ECoG amplitudes are plotted relative to response onset. iPoCG = inferior postcentral gyrus.

Figure 5

Region of interest analyses in the older group. (A) The changes of high-gamma (pink) and beta (blue) amplitudes within each region of interest are plotted relative to stimulus onset (bold line: mean; thin lines: standard error). Upper and lower horizontal bars indicate the timing when ECoG amplitudes were significantly augmented or attenuated compared to the baseline value during the resting period, respectively. ‘+0.2’ indicates 20% amplitude augmentation compared to the baseline value during the resting period. pSTG = posterior superior-temporal gyrus; iPreCG = inferior precentral gyrus; POr = pars orbitalis of the inferior-frontal gyrus. (B) The changes of ECoG amplitudes in the left hemisphere are plotted relative to stimulus offset. cMFG = caudal middle-frontal gyrus; ENT = entorhinal gyrus; IPL = inferior parietal lobule; pCC = posterior cingulate gyrus; PHG = parahippocampal gyrus; pMTG = posterior middle-temporal gyrus; pSFG = posterior superior-frontal gyrus; PTr = pars triangularis of the inferior-frontal gyrus. POp = pars opercularis of the inferior-frontal gyrus; rMFG = rostral middle-frontal gyrus; SMG = supramarginal gyrus. (C) The changes of ECoG amplitudes in the right hemisphere are plotted relative to stimulus offset. (D) The changes of ECoG amplitudes are plotted relative to response onset. iPoCG = inferior postcentral gyrus.

Figure 5

Region of interest analyses in the older group. (A) The changes of high-gamma (pink) and beta (blue) amplitudes within each region of interest are plotted relative to stimulus onset (bold line: mean; thin lines: standard error). Upper and lower horizontal bars indicate the timing when ECoG amplitudes were significantly augmented or attenuated compared to the baseline value during the resting period, respectively. ‘+0.2’ indicates 20% amplitude augmentation compared to the baseline value during the resting period. pSTG = posterior superior-temporal gyrus; iPreCG = inferior precentral gyrus; POr = pars orbitalis of the inferior-frontal gyrus. (B) The changes of ECoG amplitudes in the left hemisphere are plotted relative to stimulus offset. cMFG = caudal middle-frontal gyrus; ENT = entorhinal gyrus; IPL = inferior parietal lobule; pCC = posterior cingulate gyrus; PHG = parahippocampal gyrus; pMTG = posterior middle-temporal gyrus; pSFG = posterior superior-frontal gyrus; PTr = pars triangularis of the inferior-frontal gyrus. POp = pars opercularis of the inferior-frontal gyrus; rMFG = rostral middle-frontal gyrus; SMG = supramarginal gyrus. (C) The changes of ECoG amplitudes in the right hemisphere are plotted relative to stimulus offset. (D) The changes of ECoG amplitudes are plotted relative to response onset. iPoCG = inferior postcentral gyrus.

Figure 5

Region of interest analyses in the older group. (A) The changes of high-gamma (pink) and beta (blue) amplitudes within each region of interest are plotted relative to stimulus onset (bold line: mean; thin lines: standard error). Upper and lower horizontal bars indicate the timing when ECoG amplitudes were significantly augmented or attenuated compared to the baseline value during the resting period, respectively. ‘+0.2’ indicates 20% amplitude augmentation compared to the baseline value during the resting period. pSTG = posterior superior-temporal gyrus; iPreCG = inferior precentral gyrus; POr = pars orbitalis of the inferior-frontal gyrus. (B) The changes of ECoG amplitudes in the left hemisphere are plotted relative to stimulus offset. cMFG = caudal middle-frontal gyrus; ENT = entorhinal gyrus; IPL = inferior parietal lobule; pCC = posterior cingulate gyrus; PHG = parahippocampal gyrus; pMTG = posterior middle-temporal gyrus; pSFG = posterior superior-frontal gyrus; PTr = pars triangularis of the inferior-frontal gyrus. POp = pars opercularis of the inferior-frontal gyrus; rMFG = rostral middle-frontal gyrus; SMG = supramarginal gyrus. (C) The changes of ECoG amplitudes in the right hemisphere are plotted relative to stimulus offset. (D) The changes of ECoG amplitudes are plotted relative to response onset. iPoCG = inferior postcentral gyrus.

Figure 6

Difference in auditory naming-related high-gamma modulation in the inferior/middle frontal gyri between the older and younger groups. Orange line: mean amplitude change in the left hemisphere. Green line: mean amplitude change in the right hemisphere. ‘+0.1’ indicates 10% amplitude augmentation compared to the baseline during the resting period. Pink vertical bars denote the epochs when left-to-right asymmetry significantly differed between the older and younger groups (Bonferroni corrected P < 0.05). cMFG = caudal middle-frontal gyrus; POr = pars orbitalis of the inferior-frontal gyrus; PTr = pars triangularis of the inferior-frontal gyrus; POp = pars opercularis of the inferior-frontal gyrus; rMFG = rostral middle-frontal gyrus.