Elsevier

NeuroImage

Volume 26, Issue 2, June 2005, Pages 347-355
NeuroImage

On the human sensorimotor-cortex beta rhythm: Sources and modeling

https://doi.org/10.1016/j.neuroimage.2005.02.008Get rights and content

Abstract

Cortical oscillations in the beta band (13–35 Hz) are known to be modulated by the GABAergic agonist benzodiazepine. To investigate the mechanisms generating the ≈20-Hz oscillations in the human cortex, we administered benzodiazepines to healthy adults and monitored cortical oscillatory activity by means of magnetoencephalography. Benzodiazepine increased the power and decreased the frequency of beta oscillations over rolandic areas. Minimum current estimates indicated the effect to take place around the hand area of the primary sensorimotor cortex. Given that previous research has identified sources of the beta rhythm in the motor cortex, our results suggest that these same motor-cortex beta sources are modulated by benzodiazepine. To explore the mechanisms underlying the increase in beta power with GABAergic inhibition, we simulated a conductance-based neuronal network comprising excitatory and inhibitory neurons. The model accounts for the increase in the beta power, the widening of the spectral peak, and the slowing down of the rhythms with benzodiazepines, implemented as an increase in GABAergic conductance. We found that an increase in IPSCs onto inhibitory neurons was more important for generating neuronal synchronization in the beta band than an increase in IPSCs onto excitatory pyramidal cells.

Introduction

Oscillatory activity of the human cerebral cortex, readily monitored by electroencephalographic (EEG) and magnetoencephalographic (MEG) recordings, comprises several prominent frequency bands. The best known is the ≈10 Hz parieto-occipital “alpha” rhythm that reacts strongly to opening/closing of the eyes. The rolandic mu-rhythm is observed as spontaneous activity in healthy subjects over sensorimotor areas and has a 10-Hz and 20-Hz components that have different sources in the primary somatosensory and the motor cortex, respectively, (see Hari and Salmelin, 1997 for a review). The 20-Hz rhythm is modulated during various motor and cognitive tasks (Farmer, 1998, Hari and Salmelin, 1997). Moreover, a part of the 20-Hz motor-cortex oscillations are coherent with simultaneously recorded surface electromyogram during isometric contraction (Conway et al., 1995, Salenius et al., 1997) and have been suggested to be related to re-calibration after movements (Kilner et al., 1999). Patients with progressive myoclonus epilepsy and chronic pain display abnormal reactivity of the motor-cortex beta-range activity (Juottonen et al., 2002, Silen et al., 2000), suggesting reduced intracortical inhibition.

In clinical EEG records, rhythmic beta oscillations are observed in frontal scalp electrodes in subjects who have taken benzodiazepine-type drugs (Wanquier, 1998). Interestingly, Baker and Baker (2003) reported that cortico-muscle coherence in the beta range decreased after the application of benzodiazepines. Our experimental aim was to investigate whether benzodiazepine would modify the motor-cortex 20-Hz oscillations measured by MEG in healthy subjects. Furthermore, we were interested in finding out whether we could identify the generation site(s) of the beta-range rhythms after benzodiazepine administration. Preliminary results on this subject (Jensen et al., 2002) prompted the current study.

The primary effect of benzodiazepines is an increase in the conductance of GABA-mediated currents. It is not intuitive how the resulting increase in inhibition could increase the power of a rhythm and why that increase would be in the beta band. We use suggestions from in vitro research and computational modeling to help to provide an answer. The human beta oscillations appear to have many features in common with gamma band oscillations (30–80 Hz) observed in various animal preparations. Gamma oscillations have been modeled in vitro in the hippocampus (Towers et al., 2002, Traub et al., 1996, Whittington et al., 1995, Whittington et al., 1997a). In those preparations, the fast-spiking interneurons are important for the gamma frequency oscillations. Bacci et al. (2003) and Faulkner et al. (1999) recently showed that these are the interneurons affected by benzodiazepine-like agonists. Interestingly, Shimono et al. (2000) showed that cholinergically induced beta oscillations in hippocampal rat slice increased in power and decreased in frequency by benzodiazepine.

The computational network model we offer hypothesizes that the human beta oscillations in the sensorimotor cortex are an analogue of the gamma oscillations studied in rats. Networks of inhibitory interneurons have shown to be crucially involved in generating the gamma rhythm (Towers et al., 2002, Traub et al., 1996, Whittington et al., 1995, Whittington et al., 1997a). The main motivation for hypothesizing this analogy is the sensitivity in frequency and power of these rhythms to GABAergic agonists, suggesting a strong role to be played by the interneuronal network. The frequencies of the rhythms are affected by the size and decay time of the GABA conductance and the drive to both excitatory and inhibitory neurons. We show a parameter range in which all the behavior of the power spectrum described in the experimental findings is replicated. Specifically, modeling the effects of benzodiazepine as an increase in the strength of the GABA conductance, we show that this can increase the power in the beta frequency range, lower the frequency and broaden the range in which there is large power. We show that the major effects come about from an increase in inhibitory current to the inhibitory interneurons; instead, increase in inhibitory currents to the excitatory pyramidal cells does not increase the beta power.

Section snippets

Subjects

Magnetoencephalographic (MEG) signals were recorded from eight healthy subjects (ages 26–35 years; 3 males; 5 females) with no history of neurological disorders. Informed consent was obtained from each subject after full explanation of the study. The work had a prior approval by the ethics committee of the Helsinki Uusimaa Hospital District.

Procedure

The subjects were seated in a relaxed position under the MEG helmet. They were instructed to keep their eyes closed and relax without falling asleep while 3

Experiments

Fig. 1 shows power spectra for subject S2 before (pre-BNZ) and after (post-BNZ) benzodiazepine administration, respectively. The spectra are arranged according to sensor locations on the helmet. Each spectrum is the average calculated from two orthogonal planar gradiometers at the same position. The enlarged graphs show the spectra from a set of gradiometers over the sensorimotor cortex. In the pre-BNZ condition, the rolandic mu rhythm consists of ≈10 Hz and ≈20 Hz main frequencies. In the

Discussion

Using magnetoencephalographic recordings in humans, we observed a strong increase with benzodiazepines in the power of beta oscillations in the primary sensorimotor regions of both hemispheres. The increase in power was associated with a small decrease in the beta frequency. The beta oscillations sensitive to benzodiazepine originated from the primary sensorimotor cortex, close to the hand area. Ours is the first study to demonstrate that the 20-Hz oscillations emerging after benzodiazepine

Acknowledgments

The experimental part of the study has been financially supported by the Academy of Finland, the NWO Innovative Research Incentive Schemes with financial aid from the Netherlands Organization for Scientific Research (NWO) and by the EU's Large-Scale Facility Neuro-BIRCH III hosted at the Brain Research Unit of the Low Temperature Laboratory, Helsinki University of Technology. The theoretical parts of the study have been supported by the National Institute of Heath, National Science Foundation

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