Reduced BOLD response to periodic visual stimulation

doi:10.1016/j.neuroimage.2003.08.025

NeuroImage

Volume 21, Issue 1, January 2004, Pages 236-243

https://doi.org/10.1016/j.neuroimage.2003.08.025 Get rights and content

Abstract

The blood oxygenation level-dependent (BOLD) response to entrained neuronal firing in the human visual cortex and lateral geniculate nuclei was investigated. Periodic checkerboard flashes at a range of frequencies (4–20 Hz) were used to drive the visual cortex neurons into entrained oscillatory firing. This is compared to a checkerboard flashing aperiodically, with the same average number of flashes per unit time. A magnetoencephalography (MEG) measurement was made to confirm that the periodic paradigm elicited entrainment. We found that for frequencies of 10 and 15 Hz, the periodic stimulus gave a smaller BOLD response than for the aperiodic stimulus. Detailed investigation at 15 Hz showed that the aperiodic stimulus gave a similar BOLD increase regardless of the magnitude of jitter (±17 ms compared to ±33 ms), indicating that flashes need to be precise to at least 17 ms to maintain entrainment. This is also evidence that for aperiodic stimuli, the amplitude of the BOLD response ordinarily reflects the total number of flashes per unit time, irrespective of the precise spacing between them, suggesting that entrainment is the main cause of the BOLD reduction in the periodic condition. The results indicate that, during entrainment, there is a reduction in the neuronal metabolic demand. We suggest that because of the selective frequency band of this effect, it could be connected to synchronised reverberations around an internal feedback loop.

Introduction

The aim of this work is to establish if there is a difference in the neuronal metabolic rate during oscillatory neuronal firing (bursts at a fixed frequency) in comparison to random neuronal firing (jittered around a central frequency).

Repetitive stimulation by a periodically flickering light causes visual cortex neurons to become entrained. The neurons synchronise their firing to the frequency of the flickering light leading to strong EEG responses at that frequency (Herrmann, 2001). Of course, repetitive aperiodic stimulation will also produce synchronous firing with a frequency profile reflecting that of the stimulus. However, periodic stimulation also produces entrainment, where the bursts of firing increase in amplitude over the first few hundred milliseconds of stimulation, and become more tightly locked to the driving frequency. Multi-unit activity (MUA) recordings in the cat (Rager and Singer, 1998) detailed the effects of repetitive stimulation for a range of flicker frequencies from 2 to 50 Hz. At 2 Hz, the response was similar to that of a single flash, with brief bursts in the first 100 ms (the phasic response), a period of reduced firing and then large bursts between 200 and 600 ms (the tonic response). For higher frequencies, the initial 200–300 ms of stimulation was characterised by firing bursts of variable amplitude and an ongoing sustained response component. Following this, entrainment emerged with regular, stimulus-locked bursting patterns. During entrainment, phasic bursts increased in amplitude and the tonic response was suppressed. The amplitude of the MUA response at the driving frequency shows peaks between 4 and 8 Hz, 16 and 30 Hz, and 30 and 50 Hz, indicating enhanced entrainment. This is in accordance with earlier single-cell recordings in the macaque monkey (Foster et al., 1985), which show a similar peak response between 4 and 8 Hz to a drifting sine-wave grating. Human EEG recordings in response to flicker stimuli (Herrmann, 2001) show increased power in the steady-state potentials for driving frequencies between 6 and 20 Hz, with a weaker peak around 40 Hz.

Differences in neuronal metabolic rate can be measured by the amplitude of the blood oxygenation level-dependent (BOLD) response, using MRI (Ogawa et al., 1993). The BOLD signal is sensitive to changes in local blood flow, blood volume, and oxygen consumption as a result of neuronal activation. Differences in the BOLD amplitude between regions could reflect differences in the haemodynamic coupling and/or differences in neuronal activity. However, modulations of the BOLD amplitude in a particular region can be assumed to reflect modulations in the underlying metabolic demand due to changes in neural activity. A number of previous studies have looked at the temporal frequency tuning of neurons using BOLD measurements Ozus et al., 2001, Singh et al., 2003, Thomas and Menon, 1998 and PET Fox and Raichle, 1984, Mentis et al., 1997. The studies all show a general increase in response amplitude up to around 8 Hz, followed by either a plateau or a decrease for higher frequencies. Our study differs from these in that, rather than considering the response to periodic stimuli with increasing frequency, we focus on the difference in response between periodic and aperiodic stimuli having a constant stimulus duration.

In this work, we use a periodically flashing checkerboard stimulus to produce oscillatory entrainment in the human visual cortex. This is compared to random bursts of neuronal firing induced by a checkerboard flashing aperiodically, with the same average number of flashes per unit time. If the response to each flash is the same, the two conditions should give the same average BOLD response. However, it is expected that the periodic condition will produce neuronal entrainment, giving firing bursts of greater amplitude and reduced tonic inter-flash activity than the aperiodic condition. The BOLD amplitude change is measured for both periodic and aperiodic stimuli at a range of frequencies (4–20 Hz). The robustness of entrainment to the magnitude of the jitter is also investigated. A magnetoencephalography (MEG) recording is included to confirm that the periodic stimulus is producing entrainment.

Section snippets

Experiment 1

Six subjects took part in this experiment on the MR scanner (21–42 years of age, one female), all with normal or corrected-to-normal vision. The stimulus (see Fig. 1) consisted of 60 s of fixation cross on a black background followed by 20 s of flashing checkerboard pattern. The long rest period of 60 s is required for the BOLD signal to fully return to baseline between trials, so that the BOLD signal increase is comparable. There were two options for the flashing checkerboard: 1: periodic,

Experiment 1

Fig. 4 shows the BOLD signal change averaged over all six subjects for each condition with increasing frequency. For frequencies of 8 Hz and below, the two stimulation conditions give very similar increases in BOLD amplitude. Between 10 and 15 Hz, the aperiodic stimulus gives a higher BOLD signal change than for the periodic stimulus. A paired t test (two-tailed distribution) between the normalised amplitude increases for the periodic and aperiodic condition over all six subjects showed that

The periodic condition gives entrained oscillatory firing

The MEG response to the periodic stimulus (Fig. 5c, red) shows a strong power increase in the visual cortex at the driving frequency of the flickering stimulus, in comparison to the aperiodic condition. This indicates the presence of entrainment, with strong bursts of firing locked to the stimulus flashes. The increased firing rate of the stimulus-locked component creates an increase in synchronous firing, allowing the magnetic fields of each neuron to add up in phase, causing the increased MEG

Acknowledgements

We thank Paul Gaalman for help with the MRI scanning, Ole Jensen for help with MEG recordings, and Wolf Singer for helpful comments on this study.

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Reduced BOLD response to periodic visual stimulation

Abstract

Introduction

Section snippets

Experiment 1

Experiment 1

The periodic condition gives entrained oscillatory firing

Acknowledgements

Neuroscience

Curr. Biol.

NeuroImage

Biophys. J.

Biophys. J.

Magn. Reson. Imaging

NeuroImage

Spatial and temporal frequency selectivity of neurones in visual cortical areas V1 and V2 of the macaque monkey

J. Physiol.

Stimulus rate dependence of regional cerebral blood flow in human striate cortex, demonstrated by positron emission tomography

J. Neurophysiol.

Simultaneous EEG and fMRI of the alpha rhythm

NeuroReport

Comparison of neuronal and hemodynamic measures of the brain response to visual stimulation: an optical imaging study

Hum. Brain Mapp.