Clinical significance and developmental changes of auditory-language-related gamma activity

Abstract

Objective: We determined the clinical impact and developmental changes of auditory-language-related augmentation of gamma activity at 50-120 Hz recorded on electrocorticography (ECoG).

Methods: We analyzed data from 77 epileptic patients ranging 4-56 years in age. We determined the effects of seizure-onset zone, electrode location, and patient-age upon gamma-augmentation elicited by an auditory-naming task.

Results: Gamma-augmentation was less frequently elicited within seizure-onset sites compared to other sites. Regardless of age, gamma-augmentation most often involved the 80-100 Hz frequency band. Gamma-augmentation initially involved bilateral superior-temporal regions, followed by left-side dominant involvement in the middle-temporal, medial-temporal, inferior-frontal, dorsolateral-premotor, and medial-frontal regions and concluded with bilateral inferior-Rolandic involvement. Compared to younger patients, those older than 10 years had a larger proportion of left dorsolateral-premotor and right inferior-frontal sites showing gamma-augmentation. The incidence of a post-operative language deficit requiring speech therapy was predicted by the number of resected sites with gamma-augmentation in the superior-temporal, inferior-frontal, dorsolateral-premotor, and inferior-Rolandic regions of the left hemisphere assumed to contain essential language function (r(2) = 0.59; p = 0.001; odds ratio = 6.04 [95% confidence-interval: 2.26-16.15]).

Conclusions: Auditory-language-related gamma-augmentation can provide additional information useful to localize the primary language areas.

Significance: These results derived from a large sample of patients support the utility of auditory-language-related gamma-augmentation in presurgical evaluation.

Figure 1. Locations of subdural electrodes and auditory-language-related gamma-augmentation

(A) Regions of interest were color-coded as follows. Green: Superior-temporal region (superior-temporal gyrus involving BA 22/41/42). Yellow: Inferior-frontal region (inferior-frontal gyrus involving BA 44/45). Light-blue: Dorsolateral-premotor region (dorsolateral portion of BA 6). Pink: Inferior-Rolandic region (BA 4/3/1/2 not more than 4 cm superior from the sylvian fissure). These four regions of interest were analyzed in our previous study of 13 patients with left-hemispheric language dominance on Wada test (Kojima et al., 2012). Light-green: Middle-temporal region (middle-temporal gyrus involving BA 21/37). Purple: Medial-temporal region (parahippocampal gyrus, hippocampus, and uncus involving BA 27/28/34/35/36). Blue: Medial-frontal region (medial portion of superior-frontal and anterior-cingulate gyri involving the posterior portion of BA 24/32/33). White: ‘other’ regions. The ‘canonical language regions’ were defined as a summation of superior-temporal, inferior-frontal, dorsolateral-premotor, and inferior-Rolandic regions in the present study. (B) Subdural electrodes on each region of interest in the individual brain surface image are superimposed on the given region of interest of this schematic illustration. Red dots indicate the sites showing significant gamma-augmentation (i.e.: ‘language-related gamma sites’). Black dots indicate all remaining sites analyzed. Seizure-onset sites are not shown in this figure. The presented data are derived from 73 patients who were assumed to have essential language function remaining in the left hemisphere.

Figure 2. The effects of seizure onset and sampling location on auditory-language-related gamma-augmentation

The proportion of sites showing significant gamma-augmentation was calculated in 14 regions of interest plus 2 ‘other’ regions. The Wilcoxon signed rank test compared such a proportion in a total of 16 regions between seizure onset and non-seizure onset sites and found that the proportion of sites showing significant gamma-augmentation was smaller in the seizure onset sites across regions (p=0.004). The Fisher’s exact probability test was repeated eight times for each region of interest and suggested that significant gamma-augmentation was more frequently noted in the left compared to the right hemisphere (FDR-corrected p<0.05) except for the superior-temporal region (FDR-corrected p>0.05). The presented data are derived from 73 patients who were assumed to have essential language function remaining in the left hemisphere.

Figure 3. The effect of patient age on the spatial pattern of auditory-language-related gamma-augmentation

The proportion of sites showing significant gamma-augmentation was calculated in 14 regions of interest plus 2 ‘other’ regions in each age group (white bar: 10 years old or younger; black bar: over 10 years old). The Fisher’s exact probability test was repeated for 16 regions of interest in 73 patients with essential language function assumed to remain in the left hemisphere; the proportion of sites showing significant gamma-augmentation in the left dorsolateral-premotor, right inferior-frontal, and left ‘other’ regions was greater in the older age group (*: FDR-corrected p<0.05 on Fisher’s exact probability test). The distribution of sites showing gamma-augmentation on each age group is presented in Figure S2 on the website.

Figure 4. The effects of patient age and the peak frequency band of auditory-language-related gamma-augmentation in the left inferior-Rolandic region

Each square indicates the median of peak frequency bands of gamma-augmentations in the left inferior-Rolandic region in each of patients assumed to have essential language function remaining in the left hemisphere. Each triangle indicates that of patients assumed to have essential language function reorganized to the right hemisphere. The median of peak frequency bands of gamma-augmentations in each region of interest is listed in Table 2.

Figure 5. The temporal characteristics of auditory-language-related gamma-augmentation in the left hemisphere

The X-axis shows the time in ms, and +/− 0 ms reflects the offset of question. The Y-axis shows the average percent change of gamma-amplitudes at 80–100 Hz compared to those during the reference period 3000 to 2600 msec prior to the offset of question. Gamma-augmentation reached the peak sequentially in the superior-temporal (−230 msec prior to the stimulus offset), middle-temporal (−110 msec), inferior-frontal (50 msec), medial-temporal (110 msec), dorsolateral-premotor (210 msec), medial-frontal (290 msec), and inferior-Rolandic regions (680 msec). The presented data are derived from patients with essential language function assumed to remain in the left hemisphere.

Figure 6. Auditory-language-related gamma-augmentation in a 4-year-old boy with epilepsy

(A) Red circles indicate ‘language-related gamma sites’ (showing significant gamma-augmentation at 50–120 Hz, spanning at least 20-Hz in width and at least 20-msec in duration). (B) The results of time-frequency analyses are shown. Red: significant amplitude-augmentation prior to the preceding resting period. Blue: significant amplitude-attenuation. Significant gamma-augmentation sequentially involved the left superior-temporal (Channel #1), middle-temporal (Channel #2), medial-temporal (Channel #3), inferior-frontal (Channel #4), dorsolateral-premotor (Channel #5) and inferior-Rolandic regions (Channel #6). The left medial-frontal region was not sampled.