The idea that synchronous neural activity underlies cognition has driven an extensive body of research in human and animal neuroscience. Yet, insufficient data on intracranial electrical connectivity has precluded a direct test of this hypothesis in a whole-brain setting. Through the lens of memory encoding and retrieval processes, we construct whole-brain connectivity maps of fast gamma (30–100 Hz) and slow theta (3–8 Hz) spectral neural activity, based on data from 294 neurosurgical patients fitted with indwelling electrodes. Here we report that gamma networks desynchronize and theta networks synchronize during encoding and retrieval. Furthermore, for nearly all brain regions we studied, gamma power rises as that region desynchronizes with gamma activity elsewhere in the brain, establishing gamma as a largely asynchronous phenomenon. The abundant phenomenon of theta synchrony is positively correlated with a brain region’s gamma power, suggesting a predominant low-frequency mechanism for inter-regional communication.

High-frequency oscillations (HFO; gamma: 40–100 Hz, ripples: 100–200 Hz, and fast ripples: 250–500 Hz) have been widely studied in health and disease. These phenomena may serve as biomarkers for epileptic brain; however, a means of differentiating between pathological and normal physiological HFO is essential. We categorized task-induced physiological HFO during periods of HFO induced by a visual or motor task by measuring frequency, duration, and spectral amplitude of each event in single trial time-frequency spectra and compared them to pathological HFO similarly measured. Pathological HFO had higher mean spectral amplitude, longer mean duration, and lower mean frequency than physiological-induced HFO. In individual patients, support vector machine analysis correctly classified pathological HFO with sensitivities ranging from 70–98% and specificities >90% in all but one patient. In this patient, infrequent high-amplitude HFO were observed in the motor cortex just before movement onset in the motor task. This finding raises the possibility that in epileptic brain physiological-induced gamma can assume higher spectral amplitudes similar to those seen in pathologic HFO. This method if automated and validated could provide a step towards differentiating physiological HFO from pathological HFO and improving localization of epileptogenic brain.

High frequency oscillations are associated with normal brain function, but also increasingly recognized as potential biomarkers of the epileptogenic brain. Their role in human cognition has been predominantly studied in classical gamma frequencies (30–100 Hz), which reflect neuronal network coordination involved in attention, learning and memory. Invasive brain recordings in animals and humans demonstrate that physiological oscillations extend beyond the gamma frequency range, but their function in human cognitive processing has not been fully elucidated. Here we investigate high frequency oscillations spanning the high gamma (50–125 Hz), ripple (125–250 Hz) and fast ripple (250–500 Hz) frequency bands using intracranial recordings from 12 patients (five males and seven females, age 21–63 years) during memory encoding and recall of a series of affectively charged images. Presentation of the images induced high frequency oscillations in all three studied bands within the primary visual, limbic and higher order cortical regions in a sequence consistent with the visual processing stream. These induced oscillations were detected on individual electrodes localized in the amygdala, hippocampus and specific neocortical areas, revealing discrete oscillations of characteristic frequency, duration and latency from image presentation. Memory encoding and recall significantly modulated the number of induced high gamma, ripple and fast ripple detections in the studied structures, which was greater in the primary sensory areas during the encoding (Wilcoxon rank sum test, P = 0.002) and in the higher-order cortical association areas during the recall (Wilcoxon rank sum test, P = 0.001) of memorized images. Furthermore, the induced high gamma, ripple and fast ripple responses discriminated the encoded and the affectively charged images. In summary, our results show that high frequency oscillations, spanning a wide range of frequencies, are associated with memory processing and generated along distributed cortical and limbic brain regions. These findings support an important role for fast network synchronization in human cognition and extend our understanding of normal physiological brain activity during memory processing.

Gamma frequency activity (30–150 Hz) is induced in cognitive tasks and is thought to reflect underlying neural processes. Gamma frequency activity can be recorded directly from the human brain using intracranial electrodes implanted in patients undergoing treatment for drug-resistant epilepsy. Previous studies have independently explored narrowband oscillations in the local field potential and broadband power increases. It is not clear, however, which processes contribute to human brain gamma frequency activity, or their dynamics and roles during memory processing. Here a large dataset of intracranial recordings obtained during encoding of words from 101 patients was used to detect, characterize and compare induced gamma frequency activity events. Individual bursts of gamma frequency activity were isolated in the time-frequency domain to determine their spectral features, including peak frequency, amplitude, frequency span, and duration. We found two distinct types of gamma frequency activity events that showed either narrowband or broadband frequency spans revealing characteristic spectral properties. Narrowband events, the predominant type, were induced by word presentations following an initial induction of broadband events, which were temporally separated and selectively correlated with evoked response potentials, suggesting that they reflect different neural activities and play different roles during memory encoding. The two gamma frequency activity types were differentially modulated during encoding of subsequently recalled and forgotten words. In conclusion, we found evidence for two distinct activity types induced in the gamma frequency range during cognitive processing. Separating these two gamma frequency activity components contributes to the current understanding of electrophysiological biomarkers, and may prove useful for emerging neurotechnologies targeting, mapping and modulating distinct neurophysiological processes in normal and epileptogenic brain.

Objective: To investigate the generation, spectral characteristics, and potential clinical significance of brain activity preceding interictal epileptiform spike discharges (IEDs) recorded with intracranial EEG. Methods: Seventeen adult patients with drug-resistant temporal lobe epilepsy were implanted with intracranial electrodes as part of their evaluation for epilepsy surgery. IEDs detected on clinical macro- and research microelectrodes were analyzed using time-frequency spectral analysis. Results: Gamma frequency oscillations (30–100 Hz) often preceded IEDs in spatially confined brain areas. The gamma-IEDs were consistently observed 35 to 190 milliseconds before the epileptiform spike waveforms on individual macro- and microelectrodes. The gamma oscillations associated with IEDs had longer duration (p < 0.001) and slightly higher frequency (p = 0.045) when recorded on microelectrodes compared with clinical macroelectrodes. Although gamma-IEDs comprised only a subset of IEDs, they were strongly associated with electrodes in the seizure onset zone (SOZ) compared with the surrounding brain regions (p = 0.004), in sharp contrast to IEDs without preceding gamma oscillations that were often also detected outside of the SOZ. Similar to prior studies, isolated pathologic high-frequency oscillations in the gamma (30–100 Hz) and higher (100–600 Hz) frequency range, not associated with an IED, were also found to be associated with SOZ. Conclusions: The occurrence of locally generated gamma oscillations preceding IEDs suggests a mechanistic role for gamma in pathologic network activity generating IEDs. The results show a strong association between SOZ and gamma-IEDs. The potential clinical application of gamma-IEDs for mapping pathologic brain regions is intriguing, but will require future prospective studies.