Poststimulus undershoots in cerebral blood flow and BOLD fMRI responses are modulated by poststimulus neuronal activity

fMRI is the foremost technique for noninvasive measurement of human brain function. However, its utility is limited by an incomplete understanding of the relationship between neuronal activity and the hemodynamic response. Though the primary peak of the hemodynamic response is modulated by neuronal activity, the origin of the typically negative poststimulus signal is poorly understood and its amplitude assumed to covary with the primary response. We use simultaneous recordings of EEG with blood oxygenation level-dependent (BOLD) and cerebral blood flow (CBF) fMRI during unilateral median nerve stimulation to show that the poststimulus fMRI signal is neuronally modulated. We observe high spatial agreement between concurrent BOLD and CBF responses to median nerve stimulation, with primary signal increases in contralateral sensorimotor cortex and primary signal decreases in ipsilateral sensorimotor cortex. During the poststimulus period, the amplitude and directionality (positive/negative) of the BOLD signal in both contralateral and ipsilateral sensorimotor cortex depends on the poststimulus synchrony of 8–13 Hz EEG neuronal activity, which is often considered to reflect cortical inhibition, along with concordant changes in CBF and metabolism. Therefore we present conclusive evidence that the fMRI time course represents a hemodynamic signature of at least two distinct temporal phases of neuronal activity, substantially improving understanding of the origin of the BOLD response and increasing the potential measurements of brain function provided by fMRI. We suggest that the poststimulus EEG and fMRI responses may be required for the resetting of the entire sensory network to enable a return to resting-state activity levels.     

Synchronized delta oscillations correlate with the resting-state functional MRI signal

Synchronized low-frequency spontaneous fluctuations of the functional MRI (fMRI) signal have recently been applied to investigate large-scale neuronal networks of the brain in the absence of specific task instructions. However, the underlying neural mechanisms of these fluctuations remain largely unknown. To this end, electrophysiological recordings and resting-state fMRI measurements were conducted in alpha-chloralose-anesthetized rats. Using a seed-voxel analysis strategy, region-specific, anesthetic dose-dependent fMRI resting-state functional connectivity was detected in bilateral primary somatosensory cortex (S1FL) of the resting brain. Cortical electroencephalographic signals were also recorded from bilateral S1FL; a visual cortex locus served as a control site. Results demonstrate that, unlike the evoked fMRI response that correlates with power changes in the gamma bands, the resting-state fMRI signal correlates with the power coherence in low-frequency bands, particularly the delta band. These data indicate that hemodynamic fMRI signal differentially registers specific electrical oscillatory frequency band activity, suggesting that fMRI may be able to distinguish the ongoing from the evoked activity of the brain.     

Mental chronometry using latency-resolved functional MRI

Vascular responses to neural activity are exploited as the basis of a number of brain imaging techniques. The vascular response is thought to be too slow to resolve the temporal sequence of events involved in cognitive tasks, and hence, imaging studies of mental chronometry have relied on techniques such as the evoked potential. Using rapid functional MRI (fMRI) of single trials of two simple behavioral tasks, we demonstrate that while the microvascular response to the onset of neural activity is delayed consistently by several seconds, the relative timing between the onset of the fMRI responses in different brain areas appears preserved. We examined a number of parameters that characterize the fMRI response and determined that its onset time is best defined by the inflection point from the resting baseline. We have found that fMRI onset latencies determined in this manner correlate well with independently measurable parameters of the tasks such as reaction time or stimulus presentation time and can be used to determine the origin of processing delays during cognitive or perceptual tasks with a temporal accuracy of tens of milliseconds and spatial resolution of millimeters.     

A neural basis for inference in perceptual ambiguity

When looking at ambiguous visual stimuli, the observer experiences frequent spontaneous transitions between two competing percepts while physical stimulation remains unchanged. Despite recent advances in understanding the neural processes underlying such perceptual rivalry, a key question has remained unresolved: Does perceptual rivalry result merely from local bistability of neural activity patterns in sensory stimulus representations, or do higher-order areas play a causal role by shifting inference and, thus, initiating perceptual changes? We used functional MRI to measure brain activity while human observers reported successive spontaneous changes in perceived direction for an ambiguous apparent motion stimulus. In a control condition, the individual sequences of spontaneous perceptual switches during bistability were replayed by using a disambiguated version of the stimulus. Greater activations during spontaneous compared with stimulus-driven switches were observed in inferior frontal cortex bilaterally. Subsequent chronometric analyses of event-related signal time courses showed that, relative to activations in motion-sensitive extrastriate visual cortex, right inferior frontal cortex activation occurred earlier during spontaneous than during stimulus-driven perceptual changes. The temporal precedence of right inferior frontal activations suggests that this region participates in initiating spontaneous switches in perception during constant physical stimulation. Our findings can thus be seen as a signature of when and where the brain "makes up its mind" about competing perceptual interpretations of a given sensory input pattern.     

Intrinsic functional architecture predicts electrically evoked responses in the human brain

Adaptive brain function is characterized by dynamic interactions within and between neuronal circuits, often occurring at the time scale of milliseconds. These complex interactions between adjacent and noncontiguous brain areas depend on a functional architecture that is maintained even in the absence of input. Functional MRI studies carried out during rest (R-fMRI) suggest that this architecture is represented in low-frequency (<0.1 Hz) spontaneous fluctuations in the blood oxygen level-dependent signal that are correlated within spatially distributed networks of brain areas. These networks, collectively referred to as the brain's intrinsic functional architecture, exhibit a remarkable correspondence with patterns of task-evoked coactivation as well as maps of anatomical connectivity. Despite this striking correspondence, there is no direct evidence that this intrinsic architecture forms the scaffold that gives rise to faster processes relevant to information processing and seizure spread. Here, we demonstrate that the spatial distribution and magnitude of temporally correlated low-frequency fluctuations observed with R-fMRI during rest predict the pattern and magnitude of corticocortical evoked potentials elicited within 500 ms after single-pulse electrical stimulation of the cerebral cortex with intracranial electrodes. Across individuals, this relationship was found to be independent of the specific regions and functional systems probed. Our findings bridge the immense divide between the temporal resolutions of these distinct measures of brain function and provide strong support for the idea that the low-frequency signal fluctuations observed with R-fMRI maintain and update the intrinsic architecture underlying the brain's repertoire of functional responses.     

Image sequence reactivation in awake V4 networks

In the absence of sensory input, neuronal networks are far from being silent. Whether spontaneous changes in ongoing activity reflect previous sensory experience or stochastic fluctuations in brain activity is not well understood. Here we describe reactivation of stimulus-evoked activity in awake visual cortical networks. We found that continuous exposure to randomly flashed image sequences induces reactivation in macaque V4 cortical networks in the absence of visual stimulation. This reactivation of previously evoked activity is stimulus-specific, occurs only in the same temporal order as the original response, and strengthens with increased stimulus exposures. Importantly, cells exhibiting significant reactivation carry more information about the stimulus than cells that do not reactivate. These results demonstrate a surprising degree of experience-dependent plasticity in visual cortical networks as a result of repeated exposure to unattended information. We suggest that awake reactivation in visual cortex may underlie perceptual learning by passive stimulus exposure.     

The role of feedback in shaping neural representations in cat visual cortex

In the primary visual cortex, neurons with similar response preferences are grouped into domains forming continuous maps of stimulus orientation and direction of movement. These properties are widely believed to result from the combination of ascending and lateral interactions in the visual system. We have tested this view by examining the influence of deactivating feedback signals descending from the visuoparietal cortex on the emergence of these response properties and representations in cat area 18. We thermally deactivated the dominant motion-processing region of the visuoparietal cortex and used optical and electrophysiological methods to assay neural activity evoked in area 18 by stimulation with moving gratings and fields of coherently moving randomly distributed dots. Feedback deactivation decreased signal strength in both orientation and direction maps and virtually abolished the global layout of direction maps, whereas the basic structure of the orientation maps was preserved. These findings could be accounted for by a selective silencing of highly direction-selective neurons and by the redirection of preferences of less selective neurons. Our data suggest that signals fed back from the visuoparietal cortex strongly contribute to the emergence of direction selectivity in early visual areas. Thus we propose that higher cortical areas have significant influence over fundamental neuronal properties as they emerge in lower areas.     

Transformation of the neural code for tactile detection from thalamus to cortex

To understand how sensory-driven neural activity gives rise to perception, it is essential to characterize how various relay stations in the brain encode stimulus presence. Neurons in the ventral posterior lateral (VPL) nucleus of the somatosensory thalamus and in primary somatosensory cortex (S1) respond to vibrotactile stimulation with relatively slow modulations (∼100 ms) of their firing rate. In addition, faster modulations (∼10 ms) time-locked to the stimulus waveform are observed in both areas, but their contribution to stimulus detection is unknown. Furthermore, it is unclear whether VPL and S1 neurons encode stimulus presence with similar accuracy and via the same response features. To address these questions, we recorded single neurons while trained monkeys judged the presence or absence of a vibrotactile stimulus of variable amplitude, and their activity was analyzed with a unique decoding method that is sensitive to the time scale of the firing rate fluctuations. We found that the maximum detection accuracy of single neurons is similar in VPL and S1. However, VPL relies more heavily on fast rate modulations than S1, and as a consequence, the neural code in S1 is more tolerant: its performance degrades less when the readout method or the time scale of integration is suboptimal. Therefore, S1 neurons implement a more robust code, one less sensitive to the temporal integration window used to infer stimulus presence downstream. The differences between VPL and S1 responses signaling the appearance of a stimulus suggest a transformation of the neural code from thalamus to cortex.Detecting a stimulus involves the activation of multiple areas extending from the sensory receptors to subcortical and cortical structures (1–4), and as the signal is relayed from one layer to the next, its representation in spatiotemporal patterns of activity may change (1). Previous studies have shown that, when a tactile vibratory stimulus is presented, neurons in the ventral posterior lateral (VPL) nucleus in the somatosensory thalamus and primary somatosensory cortex (S1, areas 3b and 1) respond by modulating their firing rates computed over a time scale of hundreds of milliseconds (5–9). Because these slow firing rate modulations occurring within relatively long time windows depend on amplitude and vibration frequency, they encode these key stimulus features. In addition, to varying degrees, evoked spikes in both areas also tend to be synchronized to the waveform of the applied mechanical stimulus, which, for frequencies <40 Hz, varies on a time scale of tens of milliseconds. This entrainment, which corresponds to fast firing rate modulations, also depends on stimulus amplitude (9), and so it too carries information about stimulus presence. However, it is unknown whether both the slow (∼100 ms) and fast (∼10 ms) modulations in firing rate contribute to perceptual performance during stimulus detection. Moreover, it is not clear whether the two time scales are equally important in VPL and S1, nor whether the capacity to signal stimulus presence changes from one area to the next.To investigate these issues, we recorded activity from single neurons in the VPL nucleus and S1 cortex in monkeys trained to report the presence of a 20-Hz vibrotactile stimulus of variable amplitude. The responses were then analyzed from the point of view of an ideal observer that, based on an evoked spike train, determines whether a stimulus was presented or not in a trial; crucially, however, the observer''s performance is optimized according to a specific time scale of integration. We found that, in general, fast rate modulations are more prominent in VPL than in S1 neurons, and vice versa, slow modulations are stronger in S1 than in VPL, but despite these differences, on average, the detection accuracy of single neurons was statistically the same in both areas. Importantly, however, the neural code in S1 was more resilient than in VPL, in the sense that S1 neurons were less sensitive to the readout method and time scale of integration used to infer stimulus presence. Therefore, information is transformed—but not lost—between thalamus and S1, such that fast rate modulations closely tied to the physical stimulus are progressively discarded in favor of a slower, more tolerant rate code.     

Cerebral processing of painful oesophageal stimulation: a study based on independent component analysis of the EEG

BACKGROUND AND AIMS: Independent component analysis (ICA) of the electroencephalogram (EEG) overcomes many of the classical problems in EEG analysis. We used ICA to determine the brain responses to painful stimulation of the oesophagus. METHODS: Twelve subjects with a median age of 41 years were included. With a nasal endoscope, two series of 35 electrical stimuli at the pain threshold were given to the distal oesophagus and the EEG was subjected to ICA. The sessions were separated by 30 minutes. For each component head models, event related images, spectral perturbation, coherence analysis, and dipoles were extracted. The most valid components were found according to time/frequency information and reliability in both experiments. RESULTS: Reliable components with the most valid dipoles were found in the thalamus, insula, cingulate gyrus, and sensory cortex. Time locked activities were consistent with upstream activation of these areas, and cross coherence analysis of the sources demonstrated dynamic links in the beta(14-25 Hz) and gamma(25-50 Hz) bands between the suggested networks of neurones. The thalamic components were time and phase locked intermittently, starting around 50 ms. In the cingulate gyrus, the posterior areas were always firstly activated, followed by the middle and anterior regions. Components with dipoles in the sensory cortex were localised in several regions of the somatosensory area. CONCLUSIONS: The method gives new information relating to the localisation and dynamics between neuronal networks in the brain to pain evoked from the human oesophagus, and should be used to increase our understanding of clinical pain.     

Electrophysiological signatures of resting state networks in the human brain

Functional neuroimaging and electrophysiological studies have documented a dynamic baseline of intrinsic (not stimulus- or task-evoked) brain activity during resting wakefulness. This baseline is characterized by slow (<0.1 Hz) fluctuations of functional imaging signals that are topographically organized in discrete brain networks, and by much faster (1-80 Hz) electrical oscillations. To investigate the relationship between hemodynamic and electrical oscillations, we have adopted a completely data-driven approach that combines information from simultaneous electroencephalography (EEG) and functional magnetic resonance imaging (fMRI). Using independent component analysis on the fMRI data, we identified six widely distributed resting state networks. The blood oxygenation level-dependent signal fluctuations associated with each network were correlated with the EEG power variations of delta, theta, alpha, beta, and gamma rhythms. Each functional network was characterized by a specific electrophysiological signature that involved the combination of different brain rhythms. Moreover, the joint EEG/fMRI analysis afforded a finer physiological fractionation of brain networks in the resting human brain. This result supports for the first time in humans the coalescence of several brain rhythms within large-scale brain networks as suggested by biophysical studies.     

Three-dimensional functional magnetic resonance imaging of human brain on a clinical 1.5-T scanner.

Functional magnetic resonance imaging (fMRI) is a tool for mapping brain function that utilizes neuronal activity-induced changes in blood oxygenation. An efficient three-dimensional fMRI method is presented for imaging brain activity on conventional, widely available, 1.5-T scanners, without additional hardware. This approach uses large magnetic susceptibility weighting based on the echo-shifting principle combined with multiple gradient echoes per excitation. Motor stimulation, induced by self-paced finger tapping, reliably produced significant signal increase in the hand region of the contralateral primary motor cortex in every subject tested.     

Temporal distribution of the ganglion cell volleys in the normal rat optic nerve

We describe experiments on behaving rats with electrodes implanted on the cornea, in the optic chiasm, and on the visual cortex; in addition, two red light-emitting diodes (LED) are permanently attached to the skull over the left eye. Recordings timelocked to the LED flashes reveal both the local events at each electrode site and the orderly transfer of visual information from retina to cortex. The major finding is that every stimulus, regardless of its luminance, duration, or the state of retinal light adaptation, elicits an optic nerve volley with a latency of about 10 ms and a duration of about 300 ms. This phenomenon has not been reported previously, so far as we are aware. We conclude that the retina, which originates from the forebrain of the developing embryo, behaves like a typical brain structure: it translates, within a few hundred milliseconds, the chemical information in each pattern of bleached photoreceptors into a corresponding pattern of ganglion cell neuronal information that leaves via the optic nerve. The attributes of each rat ganglion cell appear to include whether the retinal neuropile calls on it to leave after a stimulus and, if so when, within a 300-ms poststimulus epoch. The resulting retinal analysis of the scene, on arrival at the cortical level, is presumed to participate importantly in the creation of visual perceptual experiences.     

Early fMRI responses to somatosensory and optogenetic stimulation reflect neural information flow

Blood oxygenation level–dependent (BOLD) functional magnetic resonance imaging (fMRI) has been widely used to localize brain functions. To further advance understanding of brain functions, it is critical to understand the direction of information flow, such as thalamocortical versus corticothalamic projections. For this work, we performed ultrahigh spatiotemporal resolution fMRI at 15.2 T of the mouse somatosensory network during forepaw somatosensory stimulation and optogenetic stimulation of the primary motor cortex (M1). Somatosensory stimulation induced the earliest BOLD response in the ventral posterolateral nucleus (VPL), followed by the primary somatosensory cortex (S1) and then M1 and posterior thalamic nucleus. Optogenetic stimulation of excitatory neurons in M1 induced the earliest BOLD response in M1, followed by S1 and then VPL. Within S1, the middle cortical layers responded to somatosensory stimulation earlier than the upper or lower layers, whereas the upper cortical layers responded earlier than the other two layers to optogenetic stimulation in M1. The order of early BOLD responses was consistent with the canonical understanding of somatosensory network connections and cannot be explained by regional variabilities in the hemodynamic response functions measured using hypercapnic stimulation. Our data demonstrate that early BOLD responses reflect the information flow in the mouse somatosensory network, suggesting that high-field fMRI can be used for systems-level network analyses.

Blood oxygenation level–dependent (BOLD) functional magnetic resonance imaging (fMRI) has been widely used to localize brain regions and networks associated with sensation, perception, and behavior (1–3). Different functional brain regions are connected through feedforward and feedback, ascending and descending, or bottom-up and top-down projections within the network (4). Therefore, it is critical to determine the direction of information flow to better understand brain functions. However, BOLD fMRI response, which is sensitive to vascular density and baseline physiological parameters (5), varies among brain regions and subjects (6, 7). For example, a region with large draining veins has a BOLD fMRI response that is delayed by a few seconds compared with a region that contains only capillaries within the parenchyma (8–10). Consequently, it has been argued that the order of neural events that occur within a few to tens of milliseconds of one another can be biased in fMRI dynamics due to regionally variable hemodynamic response functions (HRFs) (11).One ultimate goal of fMRI research is to demonstrate the causality and temporal sequences of neural events in humans (12). Because the contribution of capillaries to BOLD fMRI increases with the magnetic field strength, we hypothesized that early hemodynamic responses at ultrahigh fields would reflect the timing of neural activation. During forepaw somatosensory stimulation in rats, the earliest fMRI response was observed in the thalamocortical (TC) input layer 4 (L4) within the primary somatosensory cortex (S1) (13–16), suggesting that early fMRI signals reflect synaptic input. However, differences in the BOLD onset responses between layers or regions could be related to differences in their HRFs. Thus, a systematic study of different neural processing orders is crucial to determine whether the onset times of BOLD fMRI responses indeed follow the order of neural events in functional interconnected regions that include thalamic nuclei with potentially different HRFs.To investigate whether early BOLD response timing reflects the direction of neural information flow, we performed high spatiotemporal–resolution fMRI at an ultrahigh magnetic field of 15.2 T while conducting somatosensory stimulation, optogenetic stimulation, and a vascular challenge in lightly anesthetized mice. Forepaw somatosensory stimulation induced significant BOLD fMRI responses across multiple interconnected brain regions, including the ventral posterolateral nucleus (VPL), the posterior complex of the thalamic nucleus (PO), S1, and the primary motor cortex (M1) (17), among which the expected information flow is VPL → S1 → M1 (18, 19). To investigate whether the early BOLD responses were reversed when the activation sequence was reversed, we performed optogenetic stimulation of excitatory neurons in M1. In addition, to investigate whether the differences in onset times among brain regions were driven by different HRFs, we used hypercapnic challenge–induced vasodilation as a vascular control condition (20, 21). The dynamic characteristics of the BOLD responses were compared among the active somatosensory regions and among the cortical layers of S1. We found that the order of onset times among the active regions and layers clearly coincided with the known sequence of neural activation, indicating that early BOLD fMRI responses can be used to identify the direction of neural information flow.     

Computer assisted analysis of EEG, evoked potentials, EEG reactivity and heart rate variability in comatose patients

A multifunctional system for combined evaluation of EEG, visual (VEP), somatosensory (SEP) and auditory brainstem evoked potentials (BAEP) is introduced. For the light stimulation an array of light emitting diodes are used for tactile stimulation a vibration stimulus is applied to he distal digit of one finger. Stimulus-synchronous EEG segments are used for EP averaging and also for quantification of either the blocking or the activation of rhythmic EEG activity. Using this technique, alpha spindles characteristic of certain comatose states can be quantified for the first time. An important parameter is the alpha frequency, which is slowed down when there is evidence of cortical lesions, but remains unchanged in primary brain stem lesions. Comparing SEP and VEP also allows for differentiation of brain stem lesions from lesions in other areas. VEP were found to be maintained in predominant brain stem disorders. The auditory brain stem potentials and the heart rate variability are of further diagnostic significance. The importance of the individual parameters such as alpha-frequency, VEP, SEP, BAEP and alpha-spindles is demonstrated by follow-up studies in comatose patients.     

Priming with real motion biases visual cortical response to bistable apparent motion

Apparent motion quartet is an ambiguous stimulus that elicits bistable perception, with the perceived motion alternating between two orthogonal paths. In human psychophysical experiments, the probability of perceiving motion in each path is greatly enhanced by a brief exposure to real motion along that path. To examine the neural mechanism underlying this priming effect, we used voltage-sensitive dye (VSD) imaging to measure the spatiotemporal activity in the primary visual cortex (V1) of awake mice. We found that a brief real motion stimulus transiently biased the cortical response to subsequent apparent motion toward the spatiotemporal pattern representing the real motion. Furthermore, intracellular recording from V1 neurons in anesthetized mice showed a similar increase in subthreshold depolarization in the neurons representing the path of real motion. Such short-term plasticity in early visual circuits may contribute to the priming effect in bistable visual perception.In bistable perception, an ambiguous sensory stimulus gives rise to two mutually exclusive interpretations, and switches between the two percepts can occur spontaneously without any change in the visual input. Such dissociation between the sensory input and perceptual interpretation provides a unique opportunity for studying the neural correlates of conscious awareness (1, 2). A well-known example of bistable perception is that induced by apparent motion quartet, consisting of a pair of dots flashed alternately at the two diagonals of an invisible square (3). The pair of dots is perceived to move back and forth, along either the vertical or horizontal edges of the square, and the switch between these two percepts occurs spontaneously. Similar bistable perception was demonstrated in the somatosensory system using vibrotactile stimuli presented to the finger pad (4), suggesting that bistable perception of ambiguous motion is mediated by a general mechanism shared across sensory modalities.An important step in elucidating the neural mechanism underlying bistable perception is to identify the brain regions in which the neuronal activity reflects the changing perception under constant sensory stimuli. Visual psychophysical studies have shown that the perception of apparent motion along a given path impaired identification of a visual target in the path, suggesting that the illusory motion is represented explicitly by some visual neurons (5). A functional MRI (fMRI) study in human subjects has revealed apparent motion-related activity in the primary visual cortex (V1) regions retinotopically mapped to the motion path (6). During the apparent motion quartet stimulus, the fMRI signal was correlated with the perceptual switches, suggesting a neural correlate of bistable perception in V1. However, the relationship between neuronal activity and the blood-oxygen-level–dependent (BOLD) signal measured with fMRI is indirect and complex (7, 8). To understand the role of V1 in bistable perception, it is important to make direct measurements of V1 electrical activity in response to the ambiguous stimuli.In this study, we examined the contribution of V1 to the perception of apparent motion by measuring a priming effect induced by real motion. In human psychophysical experiments, we showed that a brief exposure to real motion stimulus strongly enhanced the perception of apparent motion along the same path. In voltage-sensitive dye (VSD) imaging experiments in awake mice, such a real motion stimulus caused a transient increase in the cortical activity representing the motion path during subsequent cycles of apparent motion. In vivo whole-cell recordings in anesthetized mice further revealed real motion-induced potentiation of synaptic inputs to the neurons whose receptive fields fell along the motion path. Together, these results suggest that short-term plasticity in the primary visual cortex may participate in the priming effect in bistable perception of ambiguous motion stimuli.     

EEG microstate sequences in healthy humans at rest reveal scale-free dynamics

Recent findings identified electroencephalography (EEG) microstates as the electrophysiological correlates of fMRI resting-state networks. Microstates are defined as short periods (100 ms) during which the EEG scalp topography remains quasi-stable; that is, the global topography is fixed but strength might vary and polarity invert. Microstates represent the subsecond coherent activation within global functional brain networks. Surprisingly, these rapidly changing EEG microstates correlate significantly with activity in fMRI resting-state networks after convolution with the hemodynamic response function that constitutes a strong temporal smoothing filter. We postulate here that microstate sequences should reveal scale-free, self-similar dynamics to explain this remarkable effect and thus that microstate time series show dependencies over long time ranges. To that aim, we deploy wavelet-based fractal analysis that allows determining scale-free behavior. We find strong statistical evidence that microstate sequences are scale free over six dyadic scales covering the 256-ms to 16-s range. The degree of long-range dependency is maintained when shuffling the local microstate labels but becomes indistinguishable from white noise when equalizing microstate durations, which indicates that temporal dynamics are their key characteristic. These results advance the understanding of temporal dynamics of brain-scale neuronal network models such as the global workspace model. Whereas microstates can be considered the "atoms of thoughts," the shortest constituting elements of cognition, they carry a dynamic signature that is reminiscent at characteristic timescales up to multiple seconds. The scale-free dynamics of the microstates might be the basis for the rapid reorganization and adaptation of the functional networks of the brain.     

The study of the central motor conduction time to the leg: normal findings and methodologic observations

Central motor conduction time (CMCT) is calculated by subtracting latencies from each other measured to a target muscle after transcranial brain stimulation and after stimulation of lumbar spinal nerve roots. Transcranial magnetoelectrical stimulation of the motor cortex has proved to be the most useful method. However this is not true for transcutaneous stimulation of lumbar roots. In healthy subjects electrical root stimuli given at T12/L1 produced compound muscle responses in Tibialis anterior muscles in all 18 trials. However, magnetoelectrical stimulation (100% stimulus strength) evoked responses in only 8 (Novametrix) and 12 out of 18 trials (Cadwell). Stimulation with the Digitimer D190 was less effective. Additionally compound responses after electrical root excitation were more consistent and they had a higher amplitude compared with magnetoelectrical stimulation. Regarding to these results electrical lumbar root stimulation is thought to be the advantageous method despite it is slightly more uncomfortable. Therefore normal results of CMCT to Tibialis anterior (shown in Table 1) are measured after magnetoelectrical transcranial (Digitimer D190) and transcutaneous electrical stimulation of spinal nerve roots. If the peripheral motor conduction is delayed normal values have to be adapted since CMCT is thought to involve a proximal anterior root segment. An intraspinal motor conduction time can be calculated from CMCT to upper and lower extremities.     

Behavioral performance follows the time course of neural facilitation and suppression during cued shifts of feature-selective attention

A central question in the field of attention is whether visual processing is a strictly limited resource, which must be allocated by selective attention. If this were the case, attentional enhancement of one stimulus should invariably lead to suppression of unattended distracter stimuli. Here we examine voluntary cued shifts of feature-selective attention to either one of two superimposed red or blue random dot kinematograms (RDKs) to test whether such a reciprocal relationship between enhancement of an attended and suppression of an unattended stimulus can be observed. The steady-state visual evoked potential (SSVEP), an oscillatory brain response elicited by the flickering RDKs, was measured in human EEG. Supporting limited resources, we observed both an enhancement of the attended and a suppression of the unattended RDK, but this observed reciprocity did not occur concurrently: enhancement of the attended RDK started at 220 ms after cue onset and preceded suppression of the unattended RDK by about 130 ms. Furthermore, we found that behavior was significantly correlated with the SSVEP time course of a measure of selectivity (attended minus unattended) but not with a measure of total activity (attended plus unattended). The significant deviations from a temporally synchronized reciprocity between enhancement and suppression suggest that the enhancement of the attended stimulus may cause the suppression of the unattended stimulus in the present experiment.     

Magnetic resonance imaging (MRI) detection of the murine brain response to light: temporal differentiation and negative functional MRI changes.

Using a 9.4 T MRI instrument, we have obtained images of the mouse brain response to photic stimulation during a period between deep anesthesia and the early stages of arousal. The large image enhancements we observe (often >30%) are consistent with literature results extrapolated to 9.4 T. However, there are also two unusual aspects to our findings. (i) The visual area of the brain responds only to changes in stimulus intensity, suggesting that we directly detect operations of the M visual system pathway. Such a channel has been observed in mice by invasive electrophysiology, and described in detail for primates. (ii) Along with the typical positive response in the area of the occipital portion of the brain containing the visual cortex, another area displays decreased signal intensity upon stimulation.     

Neural mechanisms for visual memory and their role in attention

Recent studies show that neuronal mechanisms for learning and memory both dynamically modulate and permanently alter the representations of visual stimuli in the adult monkey cortex. Three commonly observed neuronal effects in memory-demanding tasks are repetition suppression, enhancement, and delay activity. In repetition suppression, repeated experience with the same visual stimulus leads to both short- and long-term suppression of neuronal responses in subpopulations of visual neurons. Enhancement works in an opposite fashion, in that neuronal responses are enhanced for objects with learned behavioral relevance. Delay activity is found in tasks in which animals are required to actively hold specific information “on-line” for short periods. Repetition suppression appears to be an intrinsic property of visual cortical areas such as inferior temporal cortex and is thought to be important for perceptual learning and priming. By contrast, enhancement and delay activity may depend on feedback to temporal cortex from prefrontal cortex and are thought to be important for working memory. All of these mnemonic effects on neuronal responses bias the competitive interactions that take place between stimulus representations in the cortex when there is more than one stimulus in the visual field. As a result, memory will often determine the winner of these competitions and, thus, will determine which stimulus is attended.