Light stimulus frequency dependence of activity in the rat visual system as studied with high-resolution BOLD fMRI

The neurophysiology of the rodent visual system has mainly been investigated by invasive and ex-vivo techniques providing fragmented data. This area of research has been deprived of functional MRI studies based on blood oxygenation level dependent (BOLD) contrast, which allows a whole brain approach with a high spatial and temporal resolution. In the present study, we looked at the neurovascular response properties of the visual system of the pigmented rat, focusing on the visual cortex (VC), the superior colliculus (SC) and the flocculus-paraflocculus of the cerebellum (FL-PFL), using BOLD fMRI under domitor anesthesia. Visual stimulation was performed monocularly or binocularly while flashing light from a strobe unit was presented. For each structure, we assessed the flashing frequency that evoked the optimal BOLD response: Neither the VC nor the FL-PFL displayed frequency dependence during monocular visual stimulation, but were most sensitive to low frequencies (1-5 Hz) when flashing light was provided binocularly. The SC responded optimally to high flashing rates (8-12 Hz) during both monocular and binocular stimulation. The signal intensity changes in the VC and FL-PFL were locked to the stimulation period, whereas the BOLD response in the SC showed a similar onset but a very slow recovery at offset. The VC and FL-PFL, but not the SC, showed signs of binocular competition. The observed correlation between frequency-dependent responses of different visual areas during binocular visual presentation suggests a functional relationship between the VC and FL-PFL rather than between the SC and FL-PFL.     

Frequency-Following and Connectivity of Different Visual Areas in Response to Contrast-Reversal Stimulation

The sensitivity of visual areas to different temporal frequencies, as well as the functional connections between these areas, was examined using magnetoencephalography (MEG). Alternating circular sinusoids (0, 3.1, 8.7 and 14 Hz) were presented to foveal and peripheral locations in the visual field to target ventral and dorsal stream structures, respectively. It was hypothesized that higher temporal frequencies would preferentially activate dorsal stream structures. To determine the effect of frequency on the cortical response we analyzed the late time interval (220–770 ms) using a multi-dipole spatio-temporal analysis approach to provide source locations and timecourses for each condition. As an exploratory aspect, we performed cross-correlation analysis on the source timecourses to determine which sources responded similarly within conditions. Contrary to predictions, dorsal stream areas were not activated more frequently during high temporal frequency stimulation. However, across cortical sources the frequency-following response showed a difference, with significantly higher power at the second harmonic for the 3.1 and 8.7 Hz stimulation and at the first and second harmonics for the 14 Hz stimulation with this pattern seen robustly in area V1. Cross-correlations of the source timecourses showed that both low- and high-order visual areas, including dorsal and ventral stream areas, were significantly correlated in the late time interval. The results imply that frequency information is transferred to higher-order visual areas without translation. Despite the less complex waveforms seen in the late interval of time, the cross-correlation results show that visual, temporal and parietal cortical areas are intricately involved in late-interval visual processing.     

Contribution of visual velocity and displacement cues to human balancing of support surface tilt

Vision helps humans in controlling bipedal stance, interacting mainly with vestibular and proprioceptive cues. This study investigates how postural compensation of support surface tilt is compromised by selectively reducing visual velocity cues by stroboscopic illumination of a stationary visual scene. Healthy adult subjects were presented with pseudorandom tilt sequences in the sagittal plane (tilt frequency range 0.017–2.2 Hz; velocity amplitude spectrum constant up to a frequency of 0.6 Hz, angular displacement amplitude spectrum increasing with decreasing frequencies). Center of mass (COM) sway responses were recorded for stroboscopic illuminations at 48, 32, 16, 8, and 4 Hz, as well as under continuous illumination and with eyes closed. With strobe duration (5 ms) and mean luminance (1 lx) kept constant, visual acuity and perceived brightness remained constant and the visual scene was perceived as stationary. Yet, tilt-evoked COM excursions increased with decreasing strobe frequency in a graded way, with largest effects occurring at tilt frequencies where large tilt velocities coincided with small displacements. In addition, COM excursions were reduced at the lowest strobe frequency compared to eyes closed, with the largest effect occurring at tilt frequencies where tilt displacements were large. We conclude that two mechanisms exist, a velocity mechanism that deals with tilt compensation and is foremost affected by the stroboscopic illumination and a displacement mechanism. This compares favorably to previous findings that, transferred to a stance control model, suggest a velocity mechanism for tilt compensation and a position mechanism for gravity compensation.     

The Effect of Stimulation Frequency and Retinal Stimulus Location on Visual Evoked Potential Topography

The activity of cortical neurons is influenced by retinal stimulus location and temporal modulation. We investigated how reversal frequency of black-and-white checkerboard patterns presented in different parts of the visual field affects evoked potential topography. Visual evoked potentials were recorded from an array of 16 electrodes over the occipital cortex in 12 healthy adults. A checkerboard reversal stimulus (40′ check size) was presented with frequencies between 1.95 reversals/s and 7.81 reversals/s in the center or in the left or right hemiretina. Evoked potential fields displayed the well-known components of pattern reversal evoked activity. Computation of FFT and wavelets displayed electrical brain responses directly related to stimulation frequency. Further analysis showed that both retinal stimulus location and stimulation frequency affected visual evoked activity. Field strength as well as scalp field topography changed significantly with different reversal frequency. In addition, the pattern of lateralization of components also depended on temporal frequency of stimulation.Electrical brain activity elicited by visual stimuli shows globally similar features which are modulated by stimulus location and frequency. Our results indicate that—at least partly—different neuronal assemblies are activated by stimuli of different temporal characteristics.     

Changes in BOLD transients with visual stimuli across 1-44 Hz

The dependency of positive BOLD (PBOLD) and post-stimulus undershoot (PSU) on the temporal frequency of visual stimulation was investigated using stimulation frequencies between 1 and 44 Hz. The PBOLD peak at 8 Hz in primary visual cortex was in line with previous neuroimaging studies. In addition to the 8 Hz peak, secondary peaks were observed for stimulation frequencies at 16 and 24 Hz. These additional local peaks were contrary to earlier fMRI studies which reported either a decrease or a plateau for frequencies above 8 Hz but in line with electrophysiological results obtained in animal local field potential (LFP) measurements and human steady-state visual evoked potential (SSVEP) recordings. Our results also indicate that the dependency of PSU amplitude on stimulus frequency deviates from that of PBOLD. Although their amplitudes were correlated within the 1-13 Hz range, they changed independently at stimulation frequencies between 13 and 44 Hz. The different dependency profiles of PBOLD and PSU to stimulation frequency points to different underlying neurovascular mechanisms responsible for the generation of these BOLD transients with regard to their relation to inhibitory and excitatory neuronal activity.     

Effects of stimulus orientation on spatial frequency function of the visual evoked potential

Visual performance is better in response to vertical and horizontal stimuli than oblique ones in many visual tasks; this is called the orientation effect. In order to elucidate the electrophysiological basis of this psychophysical effect, we studied the effects of stimulus orientation on the amplitudes and latencies of visual evoked potentials (VEPs) over different spatial frequencies of the visual stimulation. VEPs to sinusoidal gratings at four orientations (vertical, horizontal, and oblique at 45 degrees and 135 degrees) with eight spatial frequencies (0.5-10.7 cycles/deg) at reversal rates of 1 Hz and 4 Hz were recorded in nine subjects. At 1-Hz stimulation, the amplitude and latency of P100 were measured. At 4-Hz stimulation, VEPs were Fourier-analyzed to obtain phase and amplitude of the second harmonic response (2F). At 1-Hz stimulation, P100 latencies were decreased for oblique stimuli compared with those for horizontal and vertical stimuli at lower spatial frequencies. Conversely, those for oblique stimuli were increased compared with those for horizontal and vertical stimuli at higher spatial frequencies. At 4-Hz stimulation, spatial tuning observed in 2F amplitude of the oblique gratings shifted to lower spatial frequencies when compared with those of vertical stimulation. The alteration of the VEP spatial frequency function caused by the oblique stimuli was in good agreement with the orientation effect observed in psychophysical studies. Our study may have a clinical implication in that VEP testing with stimuli in more than one orientation at slow and fast temporal modulations can be useful in evaluating neurological disease affecting the visual system.     

Spatial properties and direction selectivity of single neurons in area 21b of the cat

The receptive field properties of single units were assessed in area 21b of the cat visual cortex. Visual cells in this area were binocular and showed relatively large receptive fields. Most cells were strongly sensitive to the direction of drifting gratings. The mean value of the half-widths of the direction tuning curves (32 degrees ) suggests broader direction tunings than are typically found in other visual areas. The spatial frequency tuning functions were either band-pass or low-pass. Cells responded optimally to low spatial frequencies (mean =0.08c/deg) and also showed low spatial resolution (mean =0.29c/deg.). The estimated values of spatial bandwidths (mean=2.2 octaves) suggest that area 21b cells act as relatively good spatial filters. Although some cells exhibited a low contrast threshold, most cells began to respond at intermediate or high contrast values (mean threshold =15.5%). Temporal frequency tuning functions were mostly band-pass and usually broad (mean temporal bandwidth=3.3 octaves). Cells were found that responded optimally to various temporal frequencies (mean optimal temporal frequency=3.2Hz), although the majority preferred a temporal frequency below 4Hz.These results suggest that visual properties (receptive fields sizes, spatial resolution and orientation/direction selectivity) of cells in area 21b differ from those of cells previously observed in the adjoining area 21a. These differences provide evidence in support of functional distinction between these two visual areas.     

Nonlinear spatial summation and the contrast gain control of cat retinal ganglion cells.

1. We studied how responses to visual stimuli at spatially separated locations were combined by cat retinal ganglion cells. 2. The temporal signal which modulated the stimuli was a sum of sinusoids. Fourier analysis of the ganglion cell impulse train yielded first order responses at the modulation frequencies, and second order responses at sums and differences of the input frequencies. 3. Spatial stimuli were spots in the centre and periphery of the cell's receptive field. Four conditions of stimulation were used: centre alone, periphery alone, centre and periphery in phase, centre and periphery out of phase. 4. The effective first order response of the centre was defined as the response due to centre stimulation in the presence of periphery stimulation, but independent of the relative phases of the two regions. Likewise, the effective first order response of the periphery was defined as the response due to periphery in the presence of centre stimulation, but independent of the relative phases of the two regions. These effective responses may be calculated by addition and subtraction of the measured responses to the combined stimuli. 5. There was a consistent difference between the first order frequency kernal of the effective centre and the first order kernel of the centre alone. The amplitudes of the effective centre responses were diminished at low frequencies of modulation compared to the isolated centre responses. Also, the phase of the effective centre's response to high frequencies was advanced. Such non-linear interaction occurred in all ganglion cells, X or Y, but the effects were larger in Y cells. 6. In addition to spatially uniform stimuli in the periphery, spatial grating patterns were also used. These peripheral gratings affected the first order kernal of the centre even though the peripheral gratings produced no first order responses by themselves. 7. The temporal properties of the non-linear interaction of centre and periphery were probed by modulation in the periphery with single sinusoids. The most effective temporal frequencies for producing non-linear summation were: (a) 4-15 Hz when all the visual stimuli were spatially uniform, (b) 2-8 Hz when spatial grating patterns were used in the periphery. 8. The characteristics of non-linear spatial summation observed in these experiments are explained by the properties of the contrast gain control mechanism which we have previously postulated.     

Human EEG responses to 1–100 Hz flicker: resonance phenomena in visual cortex and their potential correlation to cognitive phenomena

The individual properties of visual objects, like form or color, are represented in different areas in our visual cortex. In order to perceive one coherent object, its features have to be bound together. This was found to be achieved in cat and monkey brains by temporal correlation of the firing rates of neurons which code the same object. This firing rate is predominantly observed in the gamma frequency range (approx. 30–80 Hz, mainly around 40 Hz). In addition, it has been shown in humans that stimuli which flicker at gamma frequencies are processed faster by our brains than when they flicker at different frequencies. These effects could be due to neural oscillators, which preferably oscillate at certain frequencies, so-called resonance frequencies. It is also known that neurons in visual cortex respond to flickering stimuli at the frequency of the flickering light. If neural oscillators exist with resonance frequencies, they should respond more strongly to stimulation with their resonance frequency. We performed an experiment, where ten human subjects were presented flickering light at frequencies from 1 to 100 Hz in 1-Hz steps. The event-related potentials exhibited steady-state oscillations at all frequencies up to at least 90 Hz. Interestingly, the steady-state potentials exhibited clear resonance phenomena around 10, 20, 40 and 80 Hz. This could be a potential neural basis for gamma oscillations in binding experiments. The pattern of results resembles that of multiunit activity and local field potentials in cat visual cortex. Electronic Publication     

Effect of repetitive stimulation on cortical single unit activity

Activity of single units in the visual and sensomotor cortex of an uncurarized, unanesthetized rabbit was recorded by means of two independent microelectrodes during photic stimulation at differnet frequencies. Trace effects characterized by repetition of the temporal structure of afferent stimulation and by an increase in the level of intercellular correlation were discovered mainly on analysis of distant interneuronal relations after stimulation with frequencies of 2 and 5 Hz. Stimulation at a frequency of 8 Hz did not evoke trace effects.Translated from Fiziologicheskii Zhurnal SSSR im. I. M. Sechenova, Vol. 63, No. 10, pp. 1384–1391, October, 1977.     

Human ocular following responses are plastic: evidence for control by temporal frequency-dependent cortical adaptation

Summary Optokinetic nystagmus (OKN) induced by wide-field visual stimulation was measured with and without prior adaptation to moving sinusoidal gratings. Under unadapted conditions the mean gains of the slow phases of OKN in the first 500 ms were 0.5–0.8, and the eye velocities and amplitudes had rise times with time constants of 0.1–0.2 s. By contrast, following adaptation to as little as 1 s of image motion, the magnitude of the initial gains fell and the rise times of the velocities and amplitudes increased markedly. The degree of adaptation depended on the adapting temporal frequency, the optimum adaptive frequencies being 1.7–3.4 Hz. In this range of temporal frequencies, the initial gains fell to 0.1–0.3 and the rise times for velocity and amplitude ranged from 0.4 to 7.0 s, depending on the length of the adapting period. Thus the observed changes in the time constant were up to 70-fold. Neither spatial frequency or image velocity had any marked influence on the level of adaptation. The dependence on temporal frequency rather than image velocity suggests that the motion detectors feeding the adaptive system respond to local motion-related changes in luminance. The adaptive effects were direction-selective, showing that this must also be the case for the motion detectors. The adaptive effects were observed both when the drift temporal frequency on the retina was established by artificially maintaining a fixed gaze or when the adapting temporal frequency was induced by retinal slip during OKN. Time constants for recovery from adaptation were similar to motion aftereffects measured by psychophysical and physiological methods. The results suggest a link between cortical motion adaptation and adaptive mechanisms effecting the oculomotor system.     

Frequency dependent corticofugal excitation of principal cells in the cat's dorsal lateral geniculate nucleus

Summary Excitatory postsynaptic potentials (EPSPs) were evoked in principal cells of the cat's dorsal lateral geniculate nucleus by electrical stimulation of cortico-geniculate fibres. The EPSPs had a pronounced frequency sensitivity. They were barely detectable at stimulation frequencies below 3 Hz but increased dramatically in size at higher frequencies. At 30–50 Hz their amplitude typically exceeded that of EPSPs from optic tract fibres. A prominent EPSP potentiation was also obtained with pair pulse stimulation. The findings are discussed in relation to the hypothesis that the cortico-geniculate system serves as a variable gain regulator for the visual input to the cortex.     

Three bands of oscillatory activity in the lateral geniculate nucleus of the cat visual system

Neuronal responses in the cat lateral geniculate nucleus were analyzed with respect to oscillatory components in 5930 peri-stimulus time histograms recorded in 69 neurons. Oscillatory components were observed in three frequency ranges clearly separated from each other, i.e. in a lower range between 25 and 33 Hz (mean 27.8 Hz), in a middle range between 45 and 60 Hz (mean 52.5 Hz), and in a higher range between 75 and 100 Hz (mean 84.4 Hz); temporal variance within the neuronal populations showing oscillatory characteristics increased with higher frequencies. Although the frequency ranges of the oscillatory responses were clearly separated from each other, a functional dependence between these three populations of geniculate neurons appears to be possible; the numerical relationship of approximately 1:2:3 points to the possibility of a temporal coupling between distinct neuronal populations at an early stage of visual processing.     

经颅直流电刺激对孤独症谱系障碍儿童脑电的影响研究

孤独症谱系障碍(ASD)是一种复杂的大脑神经发育障碍,其核心特征是社交障碍和刻板行为。针对孤独症儿童的脑发育异常,将新兴脑调控技术——经颅直流电刺激(tDCS)应用于孤独症儿童脑调控。共招募24名孤独症儿童参加试验,其中12名孤独症儿童接受每周2次共计10次脑调控干预,另外12名孤独症儿童接受每周2次共计10次的伪刺激,作为对照组。利用功率谱和多尺度熵算法,评估脑电的功率谱和复杂度变化。结果表明,经过调控干预后,实验组儿童干预前后4~8 Hz theta频段在全脑均有显著下降(P<0.05),其中,额叶从(1.13±0.07) dB/Hz下降到(0.96±0.06)dB/Hz,左颞叶从(1.18±0.05) dB/Hz下降到(1.03±0.07)dB/Hz,中央区从(1.43±0.06) dB/Hz下降到(1.16±0.03)dB/Hz,右颞叶从(1.14±0.09) dB/Hz下降到(0.96±0.04)dB/Hz,枕叶从(1.39±0.06) dB/Hz下降到(1.09±0.03)dB/Hz;通过计算15个尺度的熵值发现,顶叶(P3,Pz,C3,C4)、枕叶(O1)以及左侧背外侧前额叶(F3)均有显著增加。研究表明,颅直流电刺激能够以无损安全的方式实现对孤独症儿童的神经调控,改善异常脑功能,因此在孤独症的康复中有很大的应用潜力。     

Substance P release and neurokinin 1 receptor activation in the rat spinal cord increase with the firing frequency of C-fibers

Both the firing frequency of primary afferents and neurokinin 1 receptor (NK1R) internalization in dorsal horn neurons increase with the intensity of noxious stimulus. Accordingly, we studied how the pattern of firing of primary afferent influences NK1R internalization. In rat spinal cord slices, electrical stimulation of the dorsal root evoked NK1R internalization in lamina I neurons by inducing substance P release from primary afferents. The stimulation frequency had pronounced effects on NK1R internalization, which increased up to 100 Hz and then diminished abruptly at 200 Hz. Peptidase inhibitors increased NK1R internalization at frequencies below 30 Hz, indicating that peptidases limit the access of substance P to the receptor at moderate firing rates. NK1R internalization increased with number of pulses at all frequencies, but maximal internalization was substantially lower at 1–10 Hz than at 30 Hz. Pulses organized into bursts produced the same NK1R internalization as sustained 30 Hz stimulation. To determine whether substance P release induced at high stimulation frequencies was from C-fibers, we recorded compound action potentials in the sciatic nerve of anesthetized rats. We observed substantial NK1R internalization when stimulating at intensities evoking a C-elevation, but not at intensities evoking only an Aδ-elevation. Each pulse in trains at frequencies up to 100 Hz evoked a C-elevation, demonstrating that C-fibers can follow these high frequencies. C-elevation amplitudes declined progressively with increasing stimulation frequency, which was likely caused by a combination of factors including temporal dispersion. In conclusion, the instantaneous firing frequency in C-fibers determines the amount of substance P released by noxious stimuli.     

Correlation of Infants'Brain and Behavior Response to Temporal Changes in Visual Stimulation

This research was designed to test the hypothesis that a direct, parametric relationship exists between infant attention and the occipital visual evoked potential (VEP) induced by temporal frequency of visual pattern stimulation. Infants (13-weeks-old; N=32) were shown identical checkerboard patterns modulated at different rates of temporal change in a paired-comparison design and durations of orienting responses were measured. Another group of infants (13-weeks-old; N=14) were shown a series of checkerboard patterns, each modulated at a different temporal rate, and the midline occipital brain response was recorded. The results showed that behavioral attention and the signal strength/sec of the VEP are both significantly related to temporal frequency of stimulation. Furthermore, when plotted to the log₂ of temporal rate, both behavioral and neurophysiological response functions were best described by inverted U-shaped curves with similar maxima (4.8 Hz vs 5.8 Hz). These data taken together indicate that infants’visual attention and occipital brain response to temporal frequency covary and that a common neurophysiological mechanism may be involved.     

稳态视觉诱发电位频率响应特性研究

目的稳态视觉诱发电位(steady-state visual evoked potential,SSVEP)是大脑对周期性视觉刺激产生的响应,已广泛应用于基于脑电(electroencephalogram,EEG)的脑-机接口(brain-computer interface,BCI)。SSVEP频率响应曲线通常是以发光二极管(light emitting diode,LED)作为视觉刺激器的方式获得的。近年来,计算机显示器广泛用于产生闪烁刺激,然而基于计算机显示器的SSVEP频率响应曲线少有研究。为此,本文研究了基于计算机显示器的SSVEP频率响应特性。方法利用采样正弦编码方法在普通LCD显示器上产生了42个刺激频率(频率范围4~45 Hz),并收集了10位健康受试者的脑电数据,以研究SSVEP幅值/信噪比(signal-to-noise ratio,SNR)与刺激频率的关系。结果较强SSVEP响应出现在大脑枕区。SSVEP基频幅值的峰值出现在10 Hz处,且第二峰值出现在20 Hz处。SSVEP二次谐波幅值的峰值出现在6 Hz且在高刺激频率处幅值较小。低、中频段的SSVEP基频信噪比处于相当的水平。结论本文的实验结果可以为基于计算机显示器的SSVEP-BCIs的频率选择提供依据。     

Changes in the cortical silent period after repetitive magnetic stimulation of cortical motor areas

Behavioral experiments were conducted to examine the role of the cholinergic receptor-agonist muscarine or its antagonist homatropine on the mating behavior of sexually experienced male rats. Male copulatory behavior was recorded after intrathecally administered saline, muscarine (7.5 μg), or homatropine (25 μg). Changes in copulatory behavior were assessed by the following parameters: intromission latency, intromission frequency, intercopulatory interval, ejaculation latency, and postejaculatory interval. Intromission frequency, intercopulatory interval, and ejaculation latency were decreased significantly by muscarine. Intrathecal homatropine decreased the number of copulating animals (five out of 13). In the five animals that were able to ejaculate after homatropine, intromission latency, intercopulatory interval, and ejaculation latency increased significantly. The effects of both drugs on locomotion were also tested. Muscarine induced no significant changes in locomotion compared with saline. A significant increase in locomotion was found after homatropine treatment. These results suggest that acetylcholine, acting at spinal-cord muscarinic receptors, may be involved in ejaculation. Electronic Publication     

Illusory percepts of moving patterns due to discrete temporal sampling

Continuously, moving objects under continuous illumination can be seen to move in a direction opposite to their actual motion. This illusory reversed motion can be explained as due to discrete temporal sampling of the moving stimulus by the visual system. If temporal sampling lies behind the illusory motion, then the probability of illusory motion should depend on the temporal frequency of the motion stimulus. By presenting contracting bull's-eye gratings of various spatial frequencies we were able to tease apart the drift speed and temporal frequency. The prevalence of illusory percepts depended on the temporal frequency, not the speed. The data suggest that the human visual system samples the incoming stimulation at a rate near 16 Hz.     

Rate code and temporal code for frequency of whisker stimulation in rat primary and secondary somatic sensory cortex

We recorded responses to frequencies of whisker stimulation from 479 neurons in primary (S1) and secondary (S2) somatic sensory cortex of 26 urethane-anesthetized rats. Five whiskers on the right side of the snout were deflected with air puffs at seven frequencies between 1 and 18/s. In left S1 (barrels and septa) and S2, subsets of neurons (5%) responded to whisker stimulation across the entire range of frequencies with ≥1 electrical discharges/ten stimuli (full responders). In contrast, 60% of the recorded cells responded above threshold only at stimulus frequencies below 6/s and 35% remained subthreshold at all frequencies tested. Thus, the full responders are unique in that they were always responsive and appeared particularly suited to facilitate a dynamic, broadband processing of stimulus frequency. Full responders were most responsive at 1 stimulus/s, and showed greatest synchrony with whisker motion at 18 stimuli/s. The barrel cells responded with the greatest temporal accuracy between 3 and 15 stimuli/s. The septum cells responded less accurately, but maintained their accuracy at all frequencies. Only septum cells continued to increase their discharge rate with increasing stimulus frequency. The S2 cells discharged with lowest temporal accuracy modulated only by stimulus frequencies ≤6/s and exhibited the steepest decrease in discharge/stimulus with increasing stimulus frequency. Our observations suggest that full responders in the septa are well suited to encode high frequencies of whisker stimulation in timing and rate of discharge. The barrel cells, in contrast, showed the strongest temporal coding at stimulus frequencies in the middle range, and S2 cells were most sensitive to differences in low frequencies. The ubiquitous decline in discharge/stimulus in S1 and S2 may explain the decrease in blood flow observed at increasing stimulus frequency with functional imaging.