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 patient's vocalization, and iii) the pre- and post-central gyri immediately preceding and during the patient's 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.

Recent studies have suggested that cortical gamma-oscillations are tightly linked with various forms of physiological activity. In the present study, the dynamic changes of intracranially recorded median-nerve somatosensory-evoked potentials (SEPs) and somatosensory-induced gamma-oscillations were animated on a three-dimensional MR image, and the temporal and spatial characteristics of these activities were analysed in 10 children being evaluated for epilepsy surgery. Visual and quantitative assessments revealed that short-latency SEPs and somatosensory-induced gamma-oscillations predominantly involved the post-central gyrus and less intensely involved the pre-central gyrus and the anterior parietal lobule. Formation of a dipole of N20 peak with opposite polarities across the central sulcus was well delineated in animation movies. High-frequency (100-250 Hz) somatosensory-induced gamma-oscillations emerged in the post-central gyrus at 13.6-17.5 ms after median-nerve stimulation, gradually slowed down in frequency around and below 100 Hz, and progressively involved the neighbouring areas. A substantial proportion of somatosensory-induced gamma-oscillations was initially phase-locked and the proportion of a non-phase-locked component gradually increased over time. The primary motor hand areas proven by cortical stimulation frequently coincided with the sites showing the largest N20 peak and the largest somatosensory-induced gamma oscillations. In vivo animation of SEPs and somatosensory-induced gamma oscillations both may be utilized to localize the primary sensory-motor hand area in pre-surgical evaluation. The dipole on SEPs is consistent with the previously accepted notion that the cortices along the central sulcus are activated. The high-frequency somatosensory-induced gamma-oscillations in the post-central gyrus may represent the initial neural processing for external somatosensory stimuli, whereas the subsequent lower-frequency oscillations might represent the reafferent cortical activity occurring in larger cortical networks.

SUMMARYUsing intracranial electrocorticography, we determined how cortical gamma-oscillations (50-150Hz) were induced by different visual tasks in nine children with focal epilepsy. In all children, full-field stroboscopic flash-stimuli induced gamma-augmentation in the anterior-medial occipital cortex (starting on average at 31-msec after stimulus presentation) and subsequently in the lateralpolar occipital cortex; minimal gamma-augmentation was noted in the inferior occipital-temporal cortex; occipital gamma-augmentation was followed by gamma-attenuation in three children. Central-field picture-stimuli induced sustained gamma-augmentation in the lateral-polar occipital cortex (starting on average at 69-msec) and subsequently in the inferior occipital-temporal cortex in all children and in the posterior frontal cortex in three children; the anterior-medial occipital cortex showed no gamma-augmentation but rather gamma-attenuation. Electrical stimulation of the anterior-medial occipital cortex induced a phosphene in the peripheral-field or eye deviation to the contralateral side, whereas that of the lateral-polar occipital cortex induced a phosphene in the centralfield. In summary, full-field, simple and short-lasting visual information might be preferentially processed by the anterior-medial occipital cortex, and subsequently by the lateral-polar occipital cortex. Gamma-attenuation following augmentation in the striate cortex might be associated with a relative refractory-period to flash-stimuli or feed-forward inhibition by other areas. Central-field complex visual information might be processed by a network involving the lateral-polar occipital cortex and the inferior occipital-temporal cortex. A plausible interpretation of posterior-frontal gamma-augmentation during central-field picture stimuli includes activation of the frontal-eye-field for visual searching. Gamma-attenuation in the anterior-medial occipital cortex during central-field picture-stimuli might be associated with relative inattention to the peripheral visual field during central-field object visualization.

SUMMARYBoth superior temporal gyrus and inferior Rolandic area have been reported to be involved in perception and production of speech in humans. Here, we determined how these cortical structures were activated by listening and subsequent overt articulation of syllables, by measuring event-related gamma-oscillations as quantitative measures of cortical activation. Fifteen subjects were presented an auditory syllable consisting of either 'fee [fi:]', 'faa [fα:]', 'hee [hi:]', or 'haa [hα:]', and were instructed to overtly repeat each given syllable. Gamma-oscillations in the superior temporal gyrus were highly augmented during syllable-presentation, least augmented at the onset of syllablearticulation, and again highly augmented following syllable-articulation. Gamma-oscillations were augmented in the inferior Rolandic area prior to and during syllable-articulation with the onset and peak occurring earlier in the left side. Subsets of the inferior Rolandic sites, more frequently on the left side, showed differential gamma-augmentation elicited by articulation of phoneme [f] more than [h] or phoneme [i:] more than [α:]. Our observations suggest that the superior temporal gyrus may be active when externally-presented or articulated auditory stimuli are present, and may be minimally active when articulation is about to be initiated. Our novel observation of phoneme-specific differential gamma-augmentation in the inferior Rolandic area may be partially attributed to the mouth position during phoneme-articulation. Our observations support the hypothesis that positioning of the mouth to articulate phonemes is predominantly driven and/or monitored by the primary sensorimotor area on the left side.

SUMMARYHuman activities often involve hand-motor responses following external auditory-verbal commands. It has been believed that hand movements are predominantly driven by the contralateral primary sensorimotor cortex, whereas auditory-verbal information is processed in both superior temporal gyri. It remains unknown whether cortical activation in the superior temporal gyrus during an auditory-motor task is affected by laterality of hand-motor responses. Here, event-related gammaoscillations were intracranially recorded as quantitative measures of cortical activation; we determined how cortical structures were activated by auditory-cued movement using each hand in 15 patients with focal epilepsy. Auditory-verbal stimuli elicited augmentation of gamma-oscillations in a posterior portion of the superior temporal gyrus, whereas hand-motor responses elicited gammaaugmentation in the pre-and post-central gyri. The magnitudes of such gamma-augmentation in the superior temporal, pre-central and post-central gyri were significantly larger when the hand contralateral to the recorded hemisphere was required to be used for motor responses, compared to when the ipsilateral hand was. The superior temporal gyrus in each hemisphere might play a greater pivotal role when the contralateral hand needs to be used for motor responses, compared to when the ipsilateral hand does.

SUMMARYWhy do the epileptogenic foci appear hypometabolic on interictal glucose metabolism positron emission tomography (PET) in a substantial proportion of patients with focal epilepsy but appear normo-or even hyper-metabolic in others? Such observations on interictal PET have not been fully explained by the frequency of interictal spike discharges alone. In the present study using digital electrocorticography monitoring system with high-frequency sampling, we determined how well regression models using spectral ECoG measures and spike frequency derived from 651 intracranial electrode sites explained cortical glucose metabolic patterns in six children with nonlesional focal epilepsy. Univariate regression analysis demonstrated that spectral amplitudes at gamma ranges (32-64, 64-100, and 100-200 Hz) were tightly correlated with interictal glucose uptake in the given electrode site in all children. Spike frequency was negatively correlated with interictal glucose uptake in three patients, whose epileptogenic focus appeared hypometabolic and interictal epileptiform discharge often consisted of a spike followed by a subsequent delta-wave. Conversely, spike frequency was positively correlated with interictal glucose uptake in the other three patients, whose epileptogenic foci appeared more hypermetabolic compared to the surrounding regions and associated with frequent interictal spike bursts. The spatial pattern of interictal glucose metabolism in nonlesional focal epilepsy may be better explained by gamma-oscillations derived from epileptiform and physiological neuronal activities rather than the frequency of interictal epileptiform discharges alone.

SUMMARY The mechanism of altered glucose metabolism seen on positron emission tomography (PET) in focal epilepsy is not fully understood. We determined the association between interictal glucose metabolism and interictal neuronal activity, using PET and electrocorticography (ECoG) measures derived from 865 intracranial electrode sites in 11 children with focal epilepsy associated with tuberous sclerosis complex (TSC) (age: 0.5 – 16 years) undergoing epilepsy surgery. A multiple linear regression analysis was applied to each patient, to determine whether the glucose uptake at each electrode site on interictal PET was predicted by ECoG amplitude powers and interictal spike-frequency measured in the given electrode site. The regression slopes as well as R-square values (an indicator of fitness of the regression models) were finally averaged across the 11 patients. The mean regression slope for delta amplitude power was -0.0025 (95%CI: -0.0045 to -0.0004; p=0.02 based on one-sample t-test) and that for spike frequency was -0.023 (95%CI: -0.042 to -0.0038; p=0.02). On the other hand, the mean regression slopes for the remaining ECoG amplitude powers (theta, alpha, sigma, beta and gamma activities) were not significantly different from zero. The mean R-square value was 0.39. These results suggest that increased delta-slowing and frequent spike activity were independently and additively associated with glucose hypometabolism in children with focal epilepsy associated with TSC. Association between frequent interictal spike activity and low glucose metabolism may be attributed to slow-wave components following spike discharges on ECoG recording, and a substantial proportion of the variance in regional glucose metabolism on PET could be explained by electrophysiological traits derived from conventional subdural ECoG recording.

Objective The articulatory loop is a fundamental component of language function, involved in the short-term buffer of auditory information followed by its vocal reproduction. We characterized the network dynamics of the human articulatory loop, using invasive recording and stimulation. Methods We measured high-gamma activity70-110 Hz recorded intracranially when patients with epilepsy either only listened to, or listened to and then reproduced two successive tones by humming. We also conducted network analyses, and analyzed behavioral responses to cortical stimulation. Results Presentation of the initial tone elicited high-gamma augmentation bilaterally in the superior-temporal gyrus (STG) within 40 ms, and in the precentral and inferior-frontal gyri (PCG and IFG) within 160 ms after sound onset. During presentation of the second tone, high-gamma augmentation was reduced in STG but enhanced in IFG. The task requiring tone reproduction further enhanced high-gamma augmentation in PCG during and after sound presentation. Event-related causality (ERC) analysis revealed dominant flows within STG immediately after sound onset, followed by reciprocal interactions involving PCG and IFG. Measurement of cortico-cortical evoked-potentials (CCEPs) confirmed connectivity between distant high-gamma sites in the articulatory loop. High-frequency stimulation of precentral high-gamma sites in either hemisphere induced speech arrest, inability to control vocalization, or forced vocalization. Vocalization of tones was accompanied by high-gamma augmentation over larger extents of PCG. Conclusions Bilateral PCG rapidly and directly receives feed-forward signals from STG, and may promptly initiate motor planning including sub-vocal rehearsal for short-term buffering of auditory stimuli. Enhanced high-gamma augmentation in IFG during presentation of the second tone may reflect high-order processing of the tone sequence. Significance The articulatory loop employs sustained reciprocal propagation of neural activity across a network of cortical sites with strong neurophysiological connectivity.