Topography of cortical activation differs for fundamental and harmonic frequencies of the steady-state visual-evoked responses. An EEG and PET H215O study

In humans, visual flicker stimuli of graded frequency (2-90 Hz) elicit an electroencephalographic (EEG) steady-state visual-evoked response (SSVER) with the same fundamental frequency as the stimulus and, in addition, a series of harmonic responses. The fundamental component of the SSVER is generated by increased synaptic activity in primary visual cortex (V1). We set out to determine the cortical origin of the harmonic responses in humans. For this purpose, we recorded the SSVERs at 5 different frequencies (5, 10, 15, 25, and 40 Hz) and measured regional cerebral blood flow (rCBF) with positron emission tomography-H(2)(15)O at rest and during visual stimulation at the same frequencies. The rCBF contrast weighted by the amplitude of the SSVERs first harmonics showed activation of a swath of cortex perpendicular to V1, including mostly the inferior half of the parieto-occipital sulcus. This area overlapped minimally with the primary visual cortex activated by the fundamental frequency. A different method, estimating EEG cortical source current density with low-resolution brain electromagnetic tomography, gave the same results. Our finding suggests that the inferior portion of the banks of the parieto-occipital sulci contains association visual cortex involved in the processing of stimuli that can be as simple as a flickering light source.     

The effects of stimulus modality and frequency of stimulus presentation on cross-modal distraction

Selective attention produces enhanced activity (attention-related modulations [ARMs]) in cortical regions corresponding to the attended modality and suppressed activity in cortical regions corresponding to the ignored modality. However, effects of behavioral context (e.g., temporal vs. spatial tasks) and basic stimulus properties (i.e., stimulus frequency) on ARMs are not fully understood. The current study used functional magnetic resonance imaging to investigate selectively attending and responding to either a visual or auditory metronome in the presence of asynchronous cross-modal distractors of 3 different frequencies (0.5, 1, and 2 Hz). Attending to auditory information while ignoring visual distractors was generally more efficient (i.e., required coordination of a smaller network) and less effortful (i.e., decreased interference and presence of ARMs) than attending to visual information while ignoring auditory distractors. However, these effects were modulated by stimulus frequency, as attempting to ignore auditory information resulted in the obligatory recruitment of auditory cortical areas during infrequent (0.5 Hz) stimulation. Robust ARMs were observed in both visual and auditory cortical areas at higher frequencies (2 Hz), indicating that participants effectively allocated attention to more rapidly presented targets. In summary, results provide neuroanatomical correlates for the dominance of the auditory modality in behavioral contexts that are highly dependent on temporal processing.     

Different functional loops between cerebral cortex and the subthalmic area in Parkinson's disease

We investigate the extent to which functional circuits coupling cortical and subthalamic activity are multiple and segregated by frequency in untreated Parkinson's disease (PD). To this end, we recorded EEG and local field potentials (LFPs) from macroelectrodes inserted into the subthalamic nucleus area (SA) in nine awake patients following functional neurosurgery for PD. Patients were studied after overnight withdrawal of medication. Coherence between EEG and SA LFPs was apparent in the theta (3-7 Hz), alpha (8-13 Hz), lower beta (14-20 Hz) and upper beta (21-32 Hz) bands, although activity in the alpha and upper beta bands dominated. Theta coherence predominantly involved mesial and lateral areas, alpha and lower beta coherence the mesial and ipsilateral motor areas, and upper beta coherence the midline cortex. SA LFPs led EEG in the theta band. In contrast, EEG led the depth LFP in the lower and upper beta bands. SA LFP activity in the alpha band could either lead or lag EEG. Thus there are several functional sub-loops between the subthalamic area and cerebral cortical motor regions, distinguished by their frequency, cortical topography and temporal relationships. Tuning to distinct frequencies may provide a means of marking and segregating related processing, over and above any anatomical segregation of processing streams.     

Time course of competition for visual processing resources between emotional pictures and foreground task

High-arousing emotional stimuli facilitate early visual cortex, thereby acting as strong competitors for processing resources in visual cortex. The present study used an electrophysiological approach for continuously measuring the time course of competition for processing resources in the visual pathway arising from emotionally salient but task-irrelevant input while performing a foreground target detection task. Steady-state visual evoked potentials (SSVEPs) were recorded to rapidly flickering squares superimposed upon neutral and emotionally high-arousing pictures, and variations in SSVEP amplitude over time were calculated. As reflected in SSVEP amplitude and target detection rates, arousing emotional background pictures withdrew processing resources from the detection task compared with neutral ones for several hundred milliseconds after stimulus onset. SSVEP amplitude was found to bear a close temporal relationship with accurate target detection as a function of time after stimulus onset.     

Influence of changes in arterial carbon dioxide tension on the electroencephalogram and posterior tibial nerve somatosensory cortical evoked potentials during alfentanil/nitrous oxide anesthesia

The effects of variation of arterial CO2 tension (PaCO2) on the electroencephalogram (EEG) and posterior tibial nerve somatosensory cortical evoked potentials (PTN-SCEP) during opioid/N2O anesthesia have not been well documented. We studied the effects of hypocapnia (PaCO2 approximately 23 mmHg) and hypercapnia (PaCO2 approximately 50 mmHg) during steady-state alfentanil/N2O anesthesia in 16 patients. EEG and PTN-SCEP were recorded continuously, while PaCO2 was altered in 15-min intervals by varying the inspired CO2 concentration. Hypocapnia caused significant increases in power in the delta, theta, and beta bands (P less than 0.01), with the greatest increase observed in the alpha band. Relative power increased in the alpha band but remained unchanged in the delta, theta, and beta bands. Median frequency and 95% spectral edge frequency were unaltered during hypocapnia. In contrast, hypercapnia caused a significant decrease of power in the alpha and beta bands, whereas delta and theta power remained unchanged. This was reflected in a significant decrease of the 95% spectral edge frequency, from 8.9 (6.7-11.6) to 7.0 (5.6-8.6) Hz. All EEG parameters returned to normal upon restoration of normocapnia. There was a significant negative correlation between power in the alpha band and end-tidal CO2 in all patients (r = 0.47 to -0.89). PTN-SCEP latencies and amplitudes were not significantly different from control values during hypocapnia and hypercapnia. It is concluded that variations in PaCO2 within the limits 20-50 mmHg produce substantial changes in the EEG power spectrum, especially in the alpha band (8-12 Hz), but do not alter PTN-SCEP.     

Context-related frequency modulations of macaque motor cortical LFP beta oscillations

The local field potential (LFP) is a population measure, mainly reflecting local synaptic activity. Beta oscillations (12-40 Hz) occur in motor cortical LFPs, but their functional relevance remains controversial. Power modulation studies have related beta oscillations to a "resting" motor cortex, postural maintenance, attention, sensorimotor binding and planning. Frequency modulations were largely overlooked. We here describe context-related beta frequency modulations in motor cortical LFPs. Two monkeys performed a reaching task with 2 delays. The first delay demanded attention in time in expectation of the visual spatial cue, whereas the second delay involved visuomotor integration and movement preparation. The frequency in 2 beta bands (around 20 and 30 Hz) was systematically 2-5 Hz lower during cue expectancy than during visuomotor integration and preparation. Furthermore, the frequency was directionally selective during preparation, with about 3 Hz difference between preferred and nonpreferred directions. Direction decoding with frequency gave similar accuracy as with beta power, and decoding accuracy improved significantly when combining power and frequency, suggesting that frequency might provide an additional signal for brain-machine interfaces. In conclusion, multiple beta bands coexist in motor cortex, and frequency modulations within each band are as behaviorally meaningful as power modulations, reflecting the changing behavioral context and the movement direction during preparation.     

Monitoring sedation levels by EEG spectral analysis.

Real-time electroencephalographic power spectra were obtained for a group of 37 volunteers undergoing sedation with enflurane at different concentrations in air. In part one, 17 subjects were given 0.5%, 0.75%, and 1.0% for 4 min at each level, and recovery after 5 min was assessed by the Trieger method. There was considerable variation in subject response to the different doses, but adequate sedation was indicated by the presence of a strong alpha rhythm (9-11 Hz) and suppression of frequencies below 5 Hz. Overdose was indicated by an initial shift in the alpha frequency to a lower value (6-7 Hz) followed by the appearance of delta waves (0.5-4 Hz) and loss of alpha waves. In part two, 20 volunteers inhaled enflurane at 0.5% for 10 min to allow adequate absorption, followed by a 10-min recovery period. Equal numbers showed sedation or a failure to respond to enflurane at this concentration. In the responders, sedation was accompanied by a marked shift in the ratio of the power in two frequency bands: 1-4 Hz and 8-12 Hz. Progress of the frequency band power ratio followed closely the state of the subject into sedation, overdose, and recovery. This measure was further improved by the use of multivariate analysis, which showed good discrimination of the alert, sedated, and overdosed states of the subject.     

Spectral power time-courses of human sleep EEG reveal a striking discontinuity at approximately 18 Hz marking the division between NREM-specific and wake/REM-specific fast frequency activity

Spectral power time-courses over the ultradian cycle of the sleep electroencephalogram (EEG) provide a useful window for exploring the temporal correlation between cortical EEG and sub-cortical neuronal activities. Precision in the measurement of these time-courses is thus important, but it is hampered by lacunae in the definition of the frequency band limits that are in the main based on wake EEG conventions. A frequently seen discordance between the shape of the beta power time-course across the ultradian cycle and that reported for the sequential mean firing rate of brainstem-thalamic activating neurons invites a closer examination of these band limits, especially since the sleep EEG literature indicates in several studies an intriguing non-uniformity of time-course comportment across the traditional beta band frequencies. We ascribe this tentatively to the sharp reversal of slope we have seen at approximately 18 Hz in our data and that of others. Here, therefore, using data for the first four ultradian cycles from 18 healthy subjects, we apply several criteria based on changes in time-course comportment in order to examine this non-uniformity as we move in 1 Hz bins through the frequency range 14-30 Hz. The results confirm and describe in detail the striking discontinuity of shape at around 18 Hz, with only the upper range (18-30 Hz) displaying a time-course similar to that of the firing-rate changes measured in brainstem activating neurons and acknowledged to engender states of brain activation. Fast frequencies in the lower range (15-18 Hz), on the other hand, are shown to be specific to non-rapid-eye-movement sleep. Splitting the beta band at approximately 18 Hz therefore permits a significant improvement in EEG measurement and a more precise correlation with cellular activity.     

Tracking short-term auditory cortical plasticity during classical conditioning using frequency-tagged stimuli

Animal studies indicate that short-term plasticity during classical conditioning is a fast process. The temporal details of this process in humans are unknown. We employed amplitude-modulated tones in order to elicit the steady-state field (SSF). Conditioned stimulus (CS+) and CS- had a common low carrier frequency, however, differed in their high-frequency component. Low and high frequencies within one tone were modulated at 29 and 45 Hz, respectively. Mean fast Fourier transformation analysis of each single trial allowed extraction of the cortical response to these modulation frequencies, allowing to track cortical responses trial by trial. Mutilation pictures were used as unconditioned stimulus. Furthermore, heart rate and contingency awareness were assessed. Our main findings are the following: 1) A rapid (within 5 trials) enhancement of the amplitude of the high frequencies in contrast to the low frequency, while the high frequencies differentiated later (toward end of acquisition). This partially replicates rapid plasticity as shown before in animals. 2) Those participants who were less aware of the stimulus contingencies showed a relative heart rate acceleration and greater SSF increase to the CS+. This could possibly imply a stronger early amygdala activation in these participants, which then mediates the development of conditioning-related reorganization in auditory cortical areas.     

Pre- and poststimulus alpha rhythms are related to conscious visual perception: a high-resolution EEG study

Conscious and unconscious visuospatial processes have been related to parietooccipital cortical activation as revealed by late visual-evoked potentials. Here the working hypothesis was that a specific pattern of pre- and poststimulus theta (about 4-6 Hz) and alpha (about 6-12 Hz) rhythms is differently represented during conscious compared with unconscious visuospatial processes. Electroencephalographic (EEG) data (128 channels) were recorded in normal adults during a visuospatial task. A cue stimulus appeared at the right or left (equal probability) monitor side for a "threshold time" inducing about 50% of correct recognitions. It was followed (2 s) by visual go stimuli at spatially congruent or incongruent position with reference to the cue location. Left (right) mouse button was clicked if the go stimulus appeared at the left (right) monitor side. Then, subjects said "seen" if they had detected the cue stimulus or "not seen" if missed (self-report). Sources of theta and alpha rhythms during seen and not seen EEG epochs were estimated by low-resolution electromagnetic brain topography software. Results showed that the prestimulus "low-band" (about 6-10 Hz) alpha rhythms in frontal, parietal, and occipital areas were stronger in power in the seen than in the not seen trials. After the visual stimulation, the power of the "high-band" (about 10-12 Hz) alpha rhythms in parietal and occipital areas decreased more in the seen than in the not seen trials. The present results suggest that visuospatial consciousness covary--presumably with a facilitatory effect--with the power of both pre- and poststimulus alpha rhythms.     

Functional connectivity of frontal cortex in healthy and ADHD children reflected in EEG coherence

Abnormal functional brain connectivity is a candidate factor in developmental brain disorders associated with cognitive dysfunction. We analyzed a substantial (10 min per subject) record of dense array electroencephalography with spectral power and coherence methods in attention-deficit hyperactivity disorder (ADHD) (n = 42) and control (n = 21) 10- to 13-year-old children. We found topographically distinct narrow band coherence differences between subject groups: ADHD subjects showed elevated coherence in the lower alpha (8 Hz) band and reduced coherence in the upper alpha (10-11 Hz) band. The 8-Hz ADHD elevation and a 2- to 6-Hz control group coherence elevation were independent of stimulus presentation. In response to visual stimulation, the ADHD group exhibited reduced evoked potential power and elevated frontal coherence. Only the upper alpha band control group coherence elevation discriminated according to ADHD group medication status. The findings suggest a static state of deficient connectivity in ADHD and a stimulus-induced state of overconnectivity within and between frontal hemispheres.     

Oscillations in the alpha band (9-12 Hz) increase with memory load during retention in a short-term memory task

To study the role of brain oscillations in working memory, we recorded the scalp electroencephalogram (EEG) during the retention interval of a modified Sternberg task. A power spectral analysis of the EEG during the retention interval revealed a clear peak at 9-12 Hz, a frequency in the alpha band (8-13 Hz). In apparent conflict with previous ideas according to which alpha band oscillations represent brain "idling", we found that the alpha peak systematically increased with the number of items held in working memory. The enhancement was prominent over the posterior and bilateral central regions. The enhancement over posterior regions is most likely explained by the well known alpha rhythm produced close to the parietal-occipital fissure, whereas the lateral enhancement could be explained by sources in somato-motor cortex. A time-frequency analysis revealed that the enhancement was present throughout the last 2.5 s of the 2.8 s retention interval and that alpha power rapidly diminished following the probe. The load dependence and the tight temporal regulation of alpha provide strong evidence that the alpha generating system is directly or indirectly linked to the circuits responsible for working memory. Although a clear peak in the theta band (5-8 Hz) was only detectable in one subject, other lines of evidence indicate that theta occurs and also has a role in working memory. Hypotheses concerning the role of alpha band activity in working memory are discussed.     

Opposite dependencies on visual motion coherence in human area MT+ and early visual cortex

In order to understand the relationship between brain activity and visual motion perception, knowledge of the cortical areas participating in signal processing alone is insufficient. Rather knowledge on how responses vary with the characteristics of visual motion is necessary. In this study, we measured whole brain activity using magnetoencephalography in humans discriminating the global motion direction of a random dot kinematogram whose strength was systematically varied by the percentage of coherently moving dot elements. Spectral analysis revealed 2 components correlating with motion coherence. A first component in the low-frequency domain ( approximately 3 Hz), linearly increasing with motion coherence, could be attributed to visual cortex including human area middle temporal (MT) +. A second component oscillating in the alpha frequency range and emerging after stimulus offset showed the inverse dependence on motion coherence and arose from early visual cortex. Based on these results, we first of all conclude that motion coherence is reflected in the population response of human extrastriate cortex. Second, we suggest that the occipital alpha activity represents a gating mechanism protecting visual motion integration in later cortical areas from disturbing upcoming signals.     

Mechanotransduction in the cortical bone is most efficient at loading frequencies of 5-10 Hz

A dose-response relationship has been shown between loading frequency and cortical bone adaptation for frequencies of up to 10 Hz, and is presumed to persist with further increases in frequency. Studies herein aimed to investigate cortical bone adaptation to loading frequencies of 1, 5, 10, 20 and 30 Hz. Two studies were performed in adult C57BL/6 mice using the ulna axial compression-loading model. In the first study, the histomorphometric response of the ulna was studied when loaded for 120 cycles day(-1) for 3 days at one of the five frequencies and one of two load magnitudes (1.5 or 2.0 N). In the second study, the changes in ulna geometry and mechanical properties were studied following loading for 5 min day(-1), 3 days week(-1) for 4 weeks at one of the five frequencies and one of two load magnitudes (1.0 or 1.6 N). Preliminary strain gauge measurements showed that frequency had no effect on mechanical strain per unit load. In study 1, loading frequency significantly influenced bone adaptation when loading at 2.0 N, with loading at 10 Hz resulting in significantly greater adaptation than with loading at other frequencies. In study 2, loading frequency significantly influenced the change in geometry when loading at 1.6 N, with loading at 5, 10 or 30 Hz resulting in significantly greater change than with loading at 1 Hz. Loading at 5 Hz also resulted in significantly greater change than with loading at 20 Hz. No frequency effect was found on any of the mechanical properties at either load. Overall, we found cortical bone adaptation to mechanical loading to increase with increasing loading frequency up to 5-10 Hz and to plateau with frequencies beyond 10 Hz. The mechanism for this nonlinear frequency response is not known; however, based on strain gauge measurements, we do not believe it resulted from dampening associated with high frequency loading through the flexed carpal joint. The obtained findings may relate to the mechanism of mechanotransduction within the bone. This requires further investigation.     

Spectrotemporal analysis of evoked and induced electroencephalographic responses in primary auditory cortex (A1) of the awake monkey

Electroencephalography is increasingly being used to probe the functional organization of auditory cortex. Modulation of the electroencephalographic (EEG) signal by tones was examined in primary auditory cortex (A1) of awake monkeys. EEG data were measured at 4 laminar depths defined by current source density profiles evoked by best frequency (BF) tones. Midlaminar multiunit activity was used to define the tuning characteristics of A1 sites. Presentation of BF tones increased EEG power across the range of frequencies examined (4-290 Hz), with maximal effects evident within the first 100 ms after stimulus onset. The largest relative increases in EEG power generally occurred at very high gamma frequency bands (130-210 Hz). Increases in EEG power for frequencies less than 70 Hz primarily represented changes in phase-locked activity, whereas increases at higher frequencies primarily represented changes in non-phase-locked activity. Power increases in higher gamma bands were better correlated with the A1 tonotopic organization than power increases in lower frequency bands. Results were similar across the 4 laminar depths examined. These findings highlight the value of examining high-frequency EEG components in exploring the functional organization of auditory cortex and may enhance interpretation of related studies in humans.     

High-frequency activity in human visual cortex is modulated by visual motion strength

A central goal in systems neuroscience is to understand how the brain encodes the intensity of sensory features. We used whole-head magnetoencephalography to investigate whether frequency-specific neuronal activity in the human visual cortex is systematically modulated by the intensity of an elementary sensory feature such as visual motion. Visual stimulation induced a tonic increase of neuronal activity at frequencies above 50 Hz. In order to define a functional frequency band of neuronal activity, we parametrically investigated which frequency band displays the strongest monotonic increase of responses with strength of visual motion. Consistently in all investigated subjects, this analysis resulted in a functional frequency band in the high gamma range from about 60 to 100 Hz in which activity reliably increased with visual motion strength. Using distributed source reconstruction, we found that this increase of high-frequency neuronal activity originates from several extrastriate cortical regions specialized in motion processing. We conclude that high-frequency activity in the human visual motion pathway may be relevant for encoding the intensity of visual motion signals.     

Visual mental imagery induces retinotopically organized activation of early visual areas

There is a long-standing debate as to whether visual mental imagery relies entirely on symbolic (language-like) representations or also relies on depictive (picture-like) representations. We sought to discover whether visual mental imagery could evoke cortical activity with precise visual field topography (retinotopy). Participants received three conditions: the perception condition consisted of a standard retinotopic mapping procedure, where two flickering checkerboard wedges rotated around a central fixation point. The imagery and attention conditions consisted of the same stimulus, but only the outer arcs of the wedges were visible. During imagery, participants mentally reproduced the stimulus wedges, using the stimulus arcs as a guide. The attention condition required either distributed attention or focused attention to where the stimulus wedges would have been. Event-related analysis revealed that the imagery (greater than either form of attention) retinotopic maps were similar to the perception maps. Moreover, blocked analysis revealed similar perception and imagery effects in human motion processing region MT+. These results support the depictive view of visual mental imagery.     

Ketamine increases the frequency of electroencephalographic bicoherence peak on the alpha spindle area induced with propofol

Background: The reticular and thalamocortical system is known to play aprominent role in spindle wave activity, and the spindle waveis related to the sedative effects of anaesthetics. Recently,bispectral analysis of the EEG has been developed as a bettermethod to indicate nonlinear regulation including the thalamocorticalsystem linking to the cortical area. In the present study, inorder to explore the interference of ketamine with the nonlinearregulation of the sub-cortical system, we examined the effectof ketamine on spindle waves through the bispectral analysis. Methods: The study included 21 patients. Anaesthesia was induced andmaintained using a propofol-TCI system (target-controlled infusion,with target concentration 3.5 µg ml^–1). An A-2000BIS monitor was used and the raw EEG signals were collectedvia an RS232 interface on a personal computer. Bicoherence,the normalized bispectrum, and power spectrum were analysedbefore and after i.v. administration of 1 mg kg^–1 racemicketamine. Results: Propofol caused peaks in both power and bicoherence spectra,with average frequencies of 10.6 (SD 0.9) Hz and 10.7 (1.0)Hz, respectively. The addition of ketamine significantly shiftedeach peak to frequencies of 14.4 (1.4) Hz and 13.6 (1.5) Hz,respectively [P < 0.05, mean (SD)]. Conclusions: Ketamine shifted the peaks of bicoherence induced by propofolto higher frequencies. This suggests that ketamine changes the spindle rhythms through the modulation of the nonlinear sub-corticalreverberating network.     

Density-modulated t's array,a new technique of processed electroencephalogram,for monitoring the effects of midazolam and nitrous oxide during spinal anesthesia

We have investigated the utility of a new electroencephalogram (EEG) processing system, density-modulated t's array (DTA), which we have installed in a laptop personal computer together with density-modulated spectral array (DSA) for clinical monitoring. Ten patients scheduled for orthopedic operations on the lower extremities were anesthetized with 0.5% bupivacaine intrathecally, 50% nitrous oxide in oxygen by mask, and midazolam at a dose of 0.1 mg/kg intravenously. Immediately following the administration of the drugs, the power at the frequencies between 15 and 20 Hz increased. However, the power at these higher frequencies disappeared gradually and the power in the delta band and the smaller one in the alpha band became predominant. This pattern of dominant-band shift on the DSA and DTA was observed in all the patients. In three of the patients, the sedation level remained stable as judged by the absence of body movement, quiet, regular breathing and stable hemodynamics as well as steady EEG frequency distribution throughout the operations. They awoke from anesthesia rapidly on withdrawal of nitrous oxide, with return of the power at the higher frequencies. In the other seven patients, the power at the higher frequencies suddenly reappeared on the DSA and DTA during operation and slight movements of the head and upper limbs were observed with rises in blood pressure and heart rate. In three of these seven patients, the EEG change notably preceded the physiological activities by a few minutes. On the DTA, the occurrence of any significant clinical phenomenon was displayed in a color representing at value greater than ±3. The DTA, testing power changes in the EEG at each 1-Hz interval for significant difference, permits the visual and quantitative assessment of EEG changes.