Elsevier

Progress in Neurobiology

Volume 100, January 2013, Pages 1-14
Progress in Neurobiology

Theta-associated high-frequency oscillations (110–160 Hz) in the hippocampus and neocortex

https://doi.org/10.1016/j.pneurobio.2012.09.002Get rights and content

Abstract

We review recent evidence for a novel type of fast cortical oscillatory activity that occurs circumscribed between 110 and 160 Hz, which we refer to as high-frequency oscillations (HFOs). HFOs characteristically occur modulated by theta phase in the hippocampus and neocortex. HFOs can co-occur with gamma oscillations nested in the same theta cycle, in which case they typically peak at different theta phases. Despite the overlapping frequency ranges, HFOs differ from hippocampal ripple oscillations in some key characteristics, including amplitude, region of occurrence, associated behavioral state, and activity time-course (sustained vs intermittent). Recent in vitro evidence suggests that HFOs depend on fast GABAergic transmission and may also depend on axonal gap junctions. The functional role of HFOs is currently unclear. Both hippocampal and neocortical theta-HFO coupling increase during REM sleep, suggesting a role for HFOs in memory processing.

Highlights

► Theta modulates high-frequency oscillations (HFOs) in the hippocampus and neocortex. ► Theta-associated HFOs coexist with low- and high-gamma oscillations. ► HFOs, ripples, and gamma oscillations are generated by different mechanisms. ► Theta-associated HFOs are a genuine rhythm and do not reflect extracellular spikes. ► Theta-HFO coupling varies with vigilance state and may underlie cognitive processing.

Introduction

The activity of cortical networks as reflected in local field potentials (LFPs) is often oscillatory (Buzsáki, 2006). Previously described, behavior-dependent bands of cortical network activity include delta (1–4 Hz), theta (4–12 Hz), alpha (8–12 Hz), high-voltage spindle (7–12 Hz), beta (12–30 Hz), gamma (30–100 Hz), and sharp wave-associated ripple (100–250 Hz) oscillations (Buzsáki and Draguhn, 2004, Buzsáki, 2006, Wang, 2010). In addition to these well-characterized rhythms, a novel type of cortical oscillatory activity in the 110–160 Hz range has been recently described (Scheffer-Teixeira et al., 2012, Tort et al., 2008). For reasons we explain below, in this work we denote this rhythm as high-frequency oscillations (HFOs), but we note that this same pattern of oscillatory activity has also been referred to as “fast gamma” (Jackson et al., 2011, Scheffzük et al., 2011). The HFOs have been detected in LFP recordings from the hippocampus (Jackson et al., 2011, Scheffer-Teixeira et al., 2012, Tort et al., 2008) and neocortex (Scheffzük et al., 2011; see also Sirota et al., 2008). In contrast to hippocampal ripples, they characteristically occur superimposed on theta activity and are modulated by the phase of this slower rhythm. Hence we also refer to this rhythm as theta-associated HFOs.

In this review we summarize the current evidence for theta-associated HFOs, as well as present previously unpublished data. We also point to several gaps in our current knowledge about this novel rhythm and suggest future research directions that will help to elucidate its network mechanisms and potential functions.

Section snippets

Identifying HFOs by cross-frequency coupling

The recent discovery of theta-associated HFOs was mainly due to the development of computational tools for analyzing phase-amplitude coupling (PAC) between LFP oscillations of different frequencies1 (Canolty et al., 2006, Cohen, 2008, Onslow et al., 2011, Penny et al., 2008, Tort et al., 2010b). PAC is a ubiquitous phenomenon in the brain and

HFOs in the raw signal and power spectrum

Although HFOs were first identified in vivo by means of CFC tools, the existence of a sustained network rhythm in the HFO range could also be subsequently demonstrated by standard power spectral density (PSD) analysis. Namely, Scheffzük et al. (2011) and Scheffer-Teixeira et al. (2012) identified a clear PSD peak in the HFO range during behavioral states associated with theta oscillations (active waking and REM sleep) (Fig. 3a and b). Importantly, the HFO power peak reported in these studies

HFOs vs low- and high-gamma oscillations

Theta-associated HFOs can co-occur with field oscillations in the traditional gamma range (30–100 Hz) (Scheffer-Teixeira et al., 2012, Tort et al., 2008). As mentioned in the introduction, some studies have referred to the HFOs as “fast gamma” oscillations (Jackson et al., 2011, Scheffzük et al., 2011; see also Sirota et al., 2008). We prefer not to employ such terminology, however, because the existence of at least two different hippocampal gamma oscillators with peak frequency below 100 Hz has

Dependence of HFO activity on hippocampal layer

Besides having different theta phases of maximal amplitude, another characteristic distinguishing HFOs from gamma oscillations is their laminar profile in the hippocampus. Scheffer-Teixeira et al. (2012) have recently shown that theta-HFO coupling occurs mostly in superficial layers of the rat CA1 region (i.e., stratum oriens-alveus), whereas coupling between gamma and theta oscillations was found in the pyramidal layer and became strongest in stratum lacunosum-moleculare (Fig. 6a). Similar

HFOs vs ripple oscillations

Ripple oscillations are the best characterized pattern of fast oscillatory activity in the hippocampus. Ripple oscillations occur associated with synchronous discharges of CA1 pyramidal cells (Csicsvari et al., 1998), which have been implicated in the transfer of information from the hippocampus to the neocortex during memory consolidation (Buzsáki, 1989, Buzsáki, 1996, Draguhn et al., 2000, Siapas and Wilson, 1998). Ripple network patterns in CA1 may vary in peak frequency, typically spanning

Dependence of theta-HFO coupling on theta power

The strength of theta phase modulation of HFO amplitude is positively correlated with theta power; that is, periods in which theta oscillations have larger amplitude are associated with a greater level of theta-HFO coupling3 (Scheffer-Teixeira et al., 2012, Scheffzük et al., 2011, Tort et al., 2008). A positive correlation between CFC and theta amplitude can be artificially generated by

HFOs and sharp edge artifacts

CFC measures are prone to spurious results in the presence of sharp signal deflections, what we refer to as sharp edge artifacts (Kramer et al., 2008). In Fig. 8a we illustrate this phenomenon by means of a synthetic example (a sawtooth wave). Basically, the abrupt deflections of the periodic signal lead to higher frequency oscillations in the high-pass filtered version of the original signal (Fig. 8a). Although genuine high-frequency oscillations do not exist in the unfiltered signal, they

HFOs and spiking activity

We start this section by stressing the fact that we define theta-associated HFOs as a specific type of high-frequency activity that occurs in certain cortical regions bounded between 100 and 170 Hz, as inferred by CFC (Fig. 2, Fig. 4, Fig. 5, Fig. 6) and power spectral analyses (Fig. 3). That said, we note that depending on the electrode location (see below), theta phase can be found to modulate a wide range of high-frequency oscillations that are not as circumscribed as the HFOs we have been

HFOs, cognitive function and REM sleep

The functional role of theta-associated HFOs, if any, remains to be better understood. Initial evidence comes from Tort et al. (2008), who showed that hippocampal theta-HFO coupling increases during the decision-making period of a T-maze task (Fig. 10a). Importantly, the changes in CFC strength within maze runs could not be entirely accounted for by variations in theta power and running speed (Tort et al., 2008). This is an important concern since PAC is positively correlated with theta power

Possible cellular and network mechanisms underlying HFOs and theta-HFO coupling

Theta-associated HFOs are only starting to be recognized as a new type of cortical oscillations, and, given their infancy, the mechanisms underlying their generation are currently far from being understood. Jackson et al. (2011) have taken an important step forward by showing that the HFOs observed in vitro depend on fast GABAergic inhibition but not on NMDA nor AMPA/kainate glutamate receptors (Fig. 11a and b). Of note, in these same recordings gamma oscillations were sensitive to both GABAA

Conclusions and future directions

Theta-associated HFOs have been observed in different labs over the last 5 years. Above we summarized the current evidence pointing to their existence as an independent type of fast cortical activity, distinct from previously characterized rhythms such as gamma and ripple oscillations. Despite recent progress, however, several open questions remain to be addressed. Below we suggest some future directions that would help elucidating their mechanisms of generation and potential functions.

Firstly,

Acknowledgments

ABLT, RST and BCS were supported by Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), and Fundação de Apoio à Pesquisa do Estado do Rio Grande do Norte (FAPERN); AD and JB were funded by the Deutsche Forschungsgemeinschaft (SFB 636/B06) and the Bernstein Center for Computational Neurosciences. We thank the Buzsáki lab for making in vivo CA1 recordings publicly available through the Collaborative Research in

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      Citation Excerpt :

      HFO as a novel type of cortical oscillatory activity has been detected from the LFP recording of the hippocampus and neocortex. The amplitude of HFO is coupled to the phase of theta oscillation [40]. Several studies have recently reported that HFO has a role in working memory processing for information flow between the hippocampus and other areas [26,40,41].

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