Erik C. Brown

In-Vivo Animation of Auditory-Language-Induced Gamma-Oscillations in Children with Intractable Focal Epilepsy

We determined if high-frequency gamma-oscillations (50- to 150-Hz) were induced by simple auditory communication over the language network areas in children with focal epilepsy. Four children (aged 7, 9, 10 and 16 years) with intractable left-hemispheric focal epilepsy underwent extraoperative electrocorticography (ECoG) as well as language mapping using neurostimulation and auditory-language-induced gamma-oscillations on ECoG. The audible communication was recorded concurrently and integrated with ECoG recording to allow for accurate time lock on ECoG analysis. In three children, who successfully completed the auditory-language task, high-frequency gamma-augmentation sequentially involved: i) the posterior superior temporal gyrus when listening to the question, ii) the posterior lateral temporal region and the posterior frontal region in the time interval between question completion and the patients vocalization, and iii) the pre- and post-central gyri immediately preceding and during the patients vocalization. The youngest child, with attention deficits, failed to cooperate during the auditory-language task, and high-frequency gamma-augmentation was noted only in the posterior superior temporal gyrus when audible questions were given. The size of language areas suggested by statistically significant high-frequency gamma-augmentation was larger than that defined by neurostimulation. The present method can provide in vivo imaging of electrophysiological activities over the language network areas during language processes. Further studies are warranted to determine whether recording of language-induced gamma-oscillations can supplement language mapping using neurostimulation in presurgical evaluation of children with focal epilepsy.

Gamma-oscillations modulated by picture naming and word reading: Intracranial recording in epileptic patients

OBJECTIVE We measured cortical gamma-oscillations in response to visual-language tasks consisting of picture naming and word reading in an effort to better understand human visual-language pathways. METHODS We studied six patients with focal epilepsy who underwent extraoperative electrocorticography (ECoG) recording. Patients were asked to overtly name images presented sequentially in the picture naming task and to overtly read written words in the reading task. RESULTS Both tasks commonly elicited gamma-augmentation (maximally at 80-100 Hz) on ECoG in the occipital, inferior-occipital-temporal and inferior-Rolandic areas, bilaterally. Picture naming, compared to reading task, elicited greater gamma-augmentation in portions of pre-motor areas as well as occipital and inferior-occipital-temporal areas, bilaterally. In contrast, word reading elicited greater gamma-augmentation in portions of bilateral occipital, left occipital-temporal and left superior-posterior-parietal areas. Gamma-attenuation was elicited by both tasks in portions of posterior cingulate and ventral premotor-prefrontal areas bilaterally. The number of letters in a presented word was positively correlated to the degree of gamma-augmentation in the medial occipital areas. CONCLUSIONS Gamma-augmentation measured on ECoG identified cortical areas commonly and differentially involved in picture naming and reading tasks. Longer words may activate the primary visual cortex for the more peripheral field. SIGNIFICANCE The present study increases our understanding of the visual-language pathways.

Multimodality language mapping in patients with left-hemispheric language dominance on Wada test

OBJECTIVE We determined the utility of electrocorticography (ECoG) and stimulation for detecting language-related sites in patients with left-hemispheric language-dominance on Wada test. METHODS We studied 13 epileptic patients who underwent language mapping using event-related gamma-oscillations on ECoG and stimulation via subdural electrodes. Sites showing significant gamma-augmentation during an auditory-naming task were defined as language-related ECoG sites. Sites at which stimulation resulted in auditory perceptual changes, failure to verbalize a correct answer, or sensorimotor symptoms involving the mouth were defined as language-related stimulation sites. We determined how frequently these methods revealed language-related sites in the superior-temporal, inferior-frontal, dorsolateral-premotor, and inferior-Rolandic regions. RESULTS Language-related sites in the superior-temporal and inferior-frontal gyri were detected by ECoG more frequently than stimulation (p < 0.05), while those in the dorsolateral-premotor and inferior-Rolandic regions were detected by both methods equally. Stimulation of language-related ECoG sites, compared to the others, more frequently elicited language symptoms (p < 0.00001). One patient developed dysphasia requiring in-patient speech therapy following resection of the dorsolateral-premotor and inferior-Rolandic regions containing language-related ECoG sites not otherwise detected by stimulation. CONCLUSIONS Language-related gamma-oscillations may serve as an alternative biomarker of underlying language function in patients with left-hemispheric language-dominance. SIGNIFICANCE Measurement of language-related gamma-oscillations is warranted in presurgical evaluation of epileptic patients.

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

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.

How to establish causality in epilepsy surgery

Focality in electro-clinical or neuroimaging data often motivates epileptologists to consider epilepsy surgery in patients with medically-uncontrolled seizures, while not all focal findings are causally associated with the generation of epileptic seizures. With the help of Hills criteria, we have discussed how to establish causality in the context of the presurgical evaluation of epilepsy. The strengths of EEG include the ability to determine the temporal relationship between cerebral activities and clinical events; thus, scalp video-EEG is necessary in the evaluation of the majority of surgical candidates. The presence of associated ictal discharges can confirm the epileptic nature of a particular spell and whether an observed neuroimaging abnormality is causally associated with the epileptic seizure. Conversely, one should be aware that scalp EEG has a limited spatial resolution and sometimes exhibits propagated epileptiform discharges more predominantly than in situ discharges generated at the seizure-onset zone. Intraoperative or extraoperative electrocorticography (ECoG) is utilized when noninvasive presurgical evaluation, including anatomical and functional neuroimaging, fails to determine the margin between the presumed epileptogenic zone and eloquent cortex. Retrospective as well as prospective studies have reported that complete resection of the seizure-onset zone on ECoG was associated with a better seizure outcome, but not all patients became seizure-free following such resective surgery. Some retrospective studies suggested that resection of sites showing high-frequency oscillations (HFOs) at >80Hz on interictal or ictal ECoG was associated with a better seizure outcome. Others reported that functionally-important areas may generate HFOs of a physiological nature during rest as well as sensorimotor and cognitive tasks. Resection of sites showing task-related augmentation of HFOs has been reported to indeed result in functional loss following surgery. Thus, some but not all sites showing interictal HFOs are causally associated with seizure generation. Furthermore, evidence suggests that some task-related HFOs can be transiently suppressed by the prior occurrence of interictal spikes. The significance of interictal HFOs should be assessed by taking into account the eloquent cortex, seizure-onset zone, and cortical lesions. Video-EEG and ECoG generally provide useful but still limited information to establish causality in presurgical evaluation. A comprehensive assessment of data derived from multiple modalities is ultimately required for successful management.

Gamma activity modulated by picture and auditory naming tasks: Intracranial recording in patients with focal epilepsy

OBJECTIVE We measured the spatial, temporal and developmental patterns of gamma activity augmented by picture- and auditory-naming tasks and determined the clinical significance of naming-related gamma-augmentation. METHODS We studied 56 epileptic patients (age: 4-56 years) who underwent extraoperative electrocorticography. The picture-naming task consisted of naming of a visually-presented object; the auditory-naming task consisted of answering an auditorily-presented sentence question. RESULTS Naming-related gamma-augmentation at 50-120 Hz involved the modality-specific sensory cortices during stimulus presentation and inferior-Rolandic regions during responses. Gamma-augmentation in the bilateral occipital and inferior/medial-temporal regions was more intense in the picture-naming than auditory-naming task, whereas that in the bilateral superior-temporal, left middle-temporal, left inferior-parietal, and left frontal regions was more intense in the auditory-naming task. Patients above 10 years old, compared to those younger, showed more extensive gamma-augmentation in the left dorsolateral-premotor region. Resection of sites showing naming-related gamma-augmentation in the left hemisphere assumed to contain essential language function was associated with increased risk of post-operative language deficits requiring speech therapy (p < 0.05). CONCLUSIONS Measurement of gamma-augmentation elicited by either naming task was useful to predict postoperative language deficits. SIGNIFICANCE A smaller degree of frontal engagement in the picture-naming task can be explained by no requirement of syntactic processing or less working memory load. More extensive gamma-augmentation in the left dorsolateral-premotor region in older individuals may suggest more proficient processing by the mature brain.

Evaluating the arcuate fasciculus with combined diffusion-weighted MRI tractography and electrocorticography

The conventional model of language‐related brain structure describing the arcuate fasciculus as a key white matter tract providing a direct connection between Wernickes region and Brocas area has been called into question. Specifically, the inferior precentral gyrus, possessing both primary motor (Brodmann Area [BA] 4) and premotor cortex (BA 6), has been identified as a potential alternative termination. The authors initially localized cortical sites involved in language using measurement of event‐related gamma‐activity on electrocorticography (ECoG). The authors then determined whether language‐related sites of the temporal lobe were connected, via white matter structures, to the inferior frontal gyrus more tightly than to the precentral gyrus. The authors found that language‐related sites of the temporal lobe were far more likely to be directly connected to the inferior precentral gyrus through the arcuate fasciculus. Furthermore, tractography was a significant predictor of frontal language‐related ECoG findings. Analysis of an interaction between anatomy and tractography in this model revealed tractrography to have the highest predictive value for language‐related ECoG findings of the precentral gyrus. This study failed to support the conventional model of language‐related brain structure. More feasible models should include the inferior precentral gyrus as a termination of the arcuate fasciculus. The exact functional significance of direct connectivity between temporal language‐related sites and the precentral gyrus requires further study. Hum Brain Mapp 35:2333–2347, 2014.

Evaluating reverse speech as a control task with language-related gamma activity on electrocorticography

Reverse speech has often been used as a control task in brain-mapping studies of language utilizing various non-invasive modalities. The rationale is that reverse speech is comparable to forward speech in terms of auditory characteristics, while omitting the linguistic components. Thus, it may control for non-language auditory functions. This finds some support in fMRI studies indicating that reverse speech resulted in less blood-oxygen-level-dependent (BOLD) signal intensity in perisylvian regions than forward speech. We attempted to externally validate a reverse speech control task using intracranial electrocorticography (ECoG) in eight patients with intractable focal epilepsy. We studied adolescent and adult patients who underwent extraoperative ECoG prior to resective epilepsy surgery. All patients received an auditory language task during ECoG recording. Patients were presented 115 audible question stimuli, including 30 reverse speech trials. Reverse speech trials more strongly engaged bilateral superior temporal sites than did the corresponding forward speech trials. Forward speech trials elicited larger gamma-augmentation at frontal lobe sites not attributable to sensorimotor function. Other temporal and frontal sites of significant augmentation showed no significant difference between reverse and forward speech. Thus, we failed to validate reported evidence of weaker activation of temporal neocortices during reverse compared to forward speech. Superior temporal lobe engagement may indicate increased attention to reverse speech. Reverse speech does not appear to be a suitable task for the control of non-language auditory functions on ECoG.

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

Functional brain maps were first delineated in two dimensions 80 years ago. By analysing stimulation and intracranial EEG data from 100 patients with epilepsy, Nakai et al. generate 3D and 4D language maps incorporating space, time and causality. These whole-brain maps allow prediction of language areas for patients undergoing neurosurgery.

Cooing- and babbling-related gamma-oscillations during infancy: intracranial recording

We determined the spatio-temporal dynamics of intracranially-recorded gamma-oscillations modulated by spontaneous cooing and babbling, which are considered to embody pre-linguistic language behaviors during infancy. Electrocorticographic (ECoG) signals were recorded from 110 cortical sites in the right hemisphere of a 10-month-old girl with focal epilepsy. Electrocorticographic signals were time-locked to the onset of cooing or babbling. The amplitudes of gamma-oscillations during vocalizations were compared to those during preceding silent reference periods. Cooing and babbling elicited significant gamma-augmentation at 30-100 Hz at distinct sites of the inferior Rolandic region, whereas both forms of vocalizations elicited gamma-augmentation at an identical superior temporal site. The spatial, temporal and spectral characteristics of gamma-augmentation elicited by cooing and babbling were similar to those elicited by phoneme vocalization in older children and adults. Differential activation within the right inferior Rolandic region during cooing and babbling may reflect the mechanical or developmental difference between these two forms of vocalizations. The right superior temporal gyrus may participate in an auditory feedback system during vocalization.