Infraslow oscillations modulate excitability and interictal epileptic activity in the human cortex during sleep

Abstract

Human cortical activity has been intensively examined at frequencies ranging from 0.5 Hz to several hundred Hz. Recent studies have, however, reported also infraslow fluctuations in neuronal population activity, magnitude of electroencephalographic oscillations, discrete sleep events, as well as in the occurrence of interictal events. Here we use direct current electroencephalography to demonstrate large-scale infraslow oscillations in the human cortex at frequencies ranging from 0.02 to 0.2 Hz. These oscillations, which are not detectable in conventional electroencephalography because of its limited recording bandwidth (typical lower limit 0.5 Hz), were observed in widespread cortical regions. Notably, the infraslow oscillations were strongly synchronized with faster activities, as well as with the interictal epileptic events and K complexes. Our findings suggest that the infraslow oscillations represent a slow, cyclic modulation of cortical gross excitability, providing also a putative mechanism for the as yet enigmatic aggravation of epileptic activity during sleep.epilepsy ͉ slow cortical oscillations ͉ phase synchrony ͉ direct current electroencephalography ͉ full-band electroencephalography A large body of literature has characterized functional and clinical correlates of cortical oscillatory activity seen in the human electroencephalography (EEG) at frequencies ranging from 0.5 Hz to several hundred Hz (1). In addition to these relatively fast EEG oscillations, some studies have demonstrated infraslow fluctuations in, for instance, neuronal population activity (2-5), EEG power (5-9), discrete sleep events (arousals, spindles, K complexes) (9-12), as well as in the occurrence of epileptic events (4, 11, 13). These observations have raised the possibility that the human cortex may generate infraslow oscillations (ISOs) underlying such fluctuations. ISOs are not detectable in conventional EEG because of its limited recording bandwidth (typical lower limit, 0.5 Hz; ref. 1).In the present study, we used direct current (DC)-coupled EEG scalp recordings (14-16) to demonstrate that ISOs are, in fact, a salient, large-scale feature of the human EEG. They were tightly associated with a cyclic modulation of fast EEG activity as well as discrete EEG events such as K complexes and interictal activity. In analogy with recent studies demonstrating that slow delta oscillations (0.5-1 Hz) may modulate brain excitability (17, 18), our data points to a role of ISOs in the control of gross cortical excitability. Our findings also provide a window on the modulation of interictal epileptiform events (IIEs) and on sleep-epilepsy interactions in the human brain. MethodsSubjects and EEG Recording. We studied 16 subjects (four females; average age, 34.3 years; range, 16-51 years) during overnight (n ϭ 9) or daytime (n ϭ 7) sleep. This study was approved by the Human Subjects Committee of the University of Washington. Twelve subjects were recorded using a custom-made 16-channel DC-coupled EEG amplifier and Ag͞AgCl electrodes (refs....

Mesoscale infraslow spontaneous membrane potential fluctuations recapitulate high-frequency activity cortical motifs

“…Furthermore, we were not limited to only sensorimotor ROIs in our approach. The interconnected nature of the activity structure of infraslow and slow activity is consistent with a cross-frequency phase-amplitude coupling relationship that has previously been indicated for infraslow fluctuations in EEG and MEG recordings in human subjects [13][14][15]60 .…”

“…In the developing brain, electrophysiological infraslow activity in the form of neuronal activity transients or bursting activity has been linked with the development of neuronal networks 11,12 , whereas in the adult brain, infraslow activity has been demonstrated to synchronize with higher-frequency brain activity 13,14 and to correlate to variability in behavioural performance 15,16 . Renewed focus on the nature of spontaneous resting-state infraslow activity has been precipitated due to an immense proliferation of functional neuroimaging studies that have revealed much about the brain's functional organization and have identified what has been described as the brain's Default Mode Network (DMN) 17 , a network of brain structures that are coherently, highly active at rest and reduced during active task performance 18 .…”

“…Renewed focus on the nature of spontaneous resting-state infraslow activity has been precipitated due to an immense proliferation of functional neuroimaging studies that have revealed much about the brain's functional organization and have identified what has been described as the brain's Default Mode Network (DMN) 17 , a network of brain structures that are coherently, highly active at rest and reduced during active task performance 18 . The DMN may represent a consistent functional organizing principle and infraslow spontaneous activity of this kind may play a profound role in modulating and/or synchronizing higher-frequency brain activity due to cross-frequency, phase-amplitude coupling 10,13,14 . Furthermore, alterations in its structure have been linked with neurodegenerative and psychiatric disease [19][20][21] suggesting the potential for the identification of novel biomarkers and a greater understanding of both disease progression and recovery.…”

Mechanisms of physiological and epileptic HFO generation

“…Nonetheless the limits of the EEG frequency bands are fuzzy. Ultra-slow (near-DC) oscillations (Aladjalova, 1957;Vanhatalo et al, 2004) and ultra-fast frequency components have also been described. Here we concentrate primarily on the fast frequency components.…”

Neuronal oscillations in the EEG under varying cognitive load: A comparative study between slow waves and faster oscillations

“…Particularly, very low frequency oscillations (VLFOs, <0.5 Hz) have been recorded in the EEG of preterm neonates, during epileptic seizure activity (Vanhatalo et al, 2005), in attention deficit hyperactivity disorder (ADHD) (Helps et al 2008(Helps et al , 2010, and during sleep stages (Steriade et al, 1993;Vanhatalo et al, 2004). These VLFOs, first observed by Biswal et al (1995) within the motor cortex in functional magnetic resonance imaging (fMRI) blood oxygenation level dependent (BOLD) signals during rest, appear to be intrinsically generated by the brain, are most prominent during rest and may allow temporal synchronisation to promote communication across diverse brain networks (Buzsáki and Draguhn, 2004;Fransson, 2005Fransson, , 2006.…”