Search

Blood-oxygenation-level-dependent functional magnetic resonance imaging (BOLD fMRI) of cortical layers relies on the hemodynamic response and is biased toward large veins on the cortical surface. Functional changes in the cerebral metabolic rate of oxygen (ΔCMRO 2 ) may reflect neural cortical function better than BOLD fMRI, but it is unknown whether the calibrated BOLD model for functional CMRO 2 measurement remains valid at high resolution. Here, we measure laminar ΔCMRO 2 elicited by visual stimulation in macaque primary visual cortex (V1) and find that ΔCMRO 2 peaks in the middle of the cortex, in agreement with autoradiographic measures of metabolism. ΔCMRO 2 values in gray matter are similar as found previously. Reductions in CMRO 2 are associated with veins at the cortical surface, suggesting that techniques for vein removal may improve the accuracy of the model at very high resolution. However, our results show feasibility of laminar ΔCMRO 2 measurement, providing a physiologically meaningful metric of laminar functional metabolism., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Damage to the primary visual cortex (V1) leads to a visual field loss (scotoma) in the retinotopically corresponding part of the visual field. Nonetheless, a small amount of residual visual sensitivity persists within the blind field. This residual capacity has been linked to activity observed in the middle temporal area complex (V5/MT+). However, it remains unknown whether the organization of hV5/MT+ changes following early visual cortical lesions. We studied the organization of area hV5/MT+ of five patients with dense homonymous defects in a quadrant of the visual field as a result of partial V1+ or optic radiation lesions. To do so, we developed a new method, which models the boundaries of population receptive fields directly from the BOLD signal of each voxel in the visual cortex. We found responses in hV5/MT+ arising inside the scotoma for all patients and identified two possible sources of activation: 1) responses might originate from partially lesioned parts of area V1 corresponding to the scotoma, and 2) responses can also originate independent of area V1 input suggesting the existence of functional V1-bypassing pathways. Apparently, visually driven activity observed in hV5/MT+ is not sufficient to mediate conscious vision. More surprisingly, visually driven activity in corresponding regions of V1 and early extrastriate areas including hV5/MT+ did not guarantee visual perception in the group of patients with post-geniculate lesions that we examined. This suggests that the fine coordination of visual activity patterns across visual areas may be an important determinant of whether visual perception persists following visual cortical lesions., (Copyright © 2018 Elsevier Inc. All rights reserved.)

The noninvasive estimation of neuronal receptive field (RF) properties in vivo allows a detailed understanding of brain organization as well as its plasticity by longitudinal following of potential changes. Visual RFs measured invasively by electrophysiology in animal models have traditionally provided a great extent of our current knowledge about the visual brain and its disorders. Voxel-based estimates of population RF (pRF) by functional magnetic resonance imaging (fMRI) in humans revolutionized the field and have been used extensively in numerous studies. However, current methods cannot estimate single-neuron RF sizes as they reflect large populations of neurons with individual RF scatter. Here, we introduce an approach to estimate RF size using spatial frequency selectivity to checkerboard patterns. This method allowed us to obtain noninvasive, average single-neuron RF estimates over a large portion of human early visual cortex. These estimates were significantly smaller compared with prior pRF methods. Furthermore, fMRI and electrophysiology experiments in nonhuman primates demonstrated an exceptionally good match, validating the approach., Competing Interests: The authors declare no conflict of interest., (Copyright © 2019 the Author(s). Published by PNAS.)

Cholinergic neuromodulation is involved in all aspects of sensory processing and is crucial for processes such as attention, learning and memory, etc. However, despite the known roles of acetylcholine (ACh), we still do not how to disentangle ACh contributions from sensory or task-evoked changes in functional magnetic resonance imaging (fMRI). Here, we investigated the effects of local injection of ACh on fMRI and neural signals in the primary visual cortex (V1) of anesthetized macaques by combining pharmaco-based MRI (phMRI) with electrophysiological recordings, using single electrodes and electrode arrays. We found that local injection of ACh elicited two distinct profiles of fMRI and neurophysiological activity, depending on the distance from the injector. Near the injection site, we observed an increase in the baseline blood oxygen-level-dependent (BOLD) and cerebral blood flow (CBF) responses, while their visual modulation decreased. In contrast, further from the injection site, we observed an increase in the visually induced BOLD and CBF modulation without changes in baseline. Neurophysiological recordings suggest that the spatial correspondence between fMRI responses and neural activity does not change in the gamma, high-gamma, and multiunit activity (MUA) bands. The results near the injection site suggest increased inhibitory drive and decreased metabolism, contrasting to the far region. These changes are thought to reflect the kinetics of ACh and its metabolism to choline., Competing Interests: The authors declare no conflict of interest., (Copyright © 2018 the Author(s). Published by PNAS.)

Neural oscillations are ubiquitously observed in cortical activity, and are widely believed to be crucial for mediating transmission of information across the cortex. Yet, the neural phenomena contributing to each oscillation band, and their effect on information coding and transmission, are largely unknown. Here, we investigated whether individual frequency bands specifically reflect changes in the concentrations of dopamine, an important neuromodulator, and how dopamine affects oscillatory information processing. We recorded the local field potential (LFP) at different depths of primary visual cortex (V1) in anesthetized monkeys (Macaca mulatta) during spontaneous activity and during visual stimulation with Hollywood movie clips while pharmacologically mimicking dopaminergic neuromodulation by systemic injection of L-DOPA (a metabolic precursor of dopamine). We found that dopaminergic neuromodulation had marked effects on both spontaneous and movie-evoked neural activity. During spontaneous activity, dopaminergic neuromodulation increased the power of the LFP specifically in the [19-38 Hz] band, suggesting that the power of endogenous visual cortex oscillations in this band can be used as a robust marker of dopaminergic neuromodulation. Moreover, dopamine increased visual information encoding over all frequencies during movie stimulation. The information increase due to dopamine was prominent in the supragranular layers of cortex that project to higher cortical areas and in the gamma [50-100 Hz] band that has been previously implicated in mediating feedforward information transfer. These results thus individuate new neural mechanisms by which dopamine may promote the readout of relevant sensory information by strengthening the transmission of information from primary to higher areas., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Functional brain development is not well understood. In the visual system, neurophysiological studies in nonhuman primates show quite mature neuronal properties near birth although visual function is itself quite immature and continues to develop over many months or years after birth. Our goal was to assess the relative development of two main visual processing streams, dorsal and ventral, using BOLD fMRI in an attempt to understand the global mechanisms that support the maturation of visual behavior. Seven infant macaque monkeys (Macaca mulatta) were repeatedly scanned, while anesthetized, over an age range of 102 to 1431 days. Large rotating checkerboard stimuli induced BOLD activation in visual cortices at early ages. Additionally we used static and dynamic Glass pattern stimuli to probe BOLD responses in primary visual cortex and two extrastriate areas: V4 and MT-V5. The resulting activations were analyzed with standard GLM and multivoxel pattern analysis (MVPA) approaches. We analyzed three contrasts: Glass pattern present/absent, static/dynamic Glass pattern presentation, and structured/random Glass pattern form. For both GLM and MVPA approaches, robust coherent BOLD activation appeared relatively late in comparison to the maturation of known neuronal properties and the development of behavioral sensitivity to Glass patterns. Robust differential activity to Glass pattern present/absent and dynamic/static stimulus presentation appeared first in V1, followed by V4 and MT-V5 at older ages; there was no reliable distinction between the two extrastriate areas. A similar pattern of results was obtained with the two analysis methods, although MVPA analysis showed reliable differential responses emerging at later ages than GLM. Although BOLD responses to large visual stimuli are detectable, our results with more refined stimuli indicate that global BOLD activity changes as behavioral performance matures. This reflects an hierarchical development of the visual pathways. Since fMRI BOLD reflects neural activity on a population level, our results indicate that, although individual neurons might be adult-like, a longer maturation process takes place on a population level.

Electrical microstimulation and more recently optogenetics are widely used to map large-scale brain circuits. However, the neuronal specificity achieved with both methods is not well understood. Here we compare cell-targeted optogenetics and electrical microstimulation in the macaque monkey brain to functionally map the koniocellular lateral geniculate nucleus (LGN) projection to primary visual cortex (V1). Selective activation of the LGN konio neurons with CamK-specific optogenetics caused selective electrical current inflow in the supra-granular layers of V1. Electrical microstimulation targeted at LGN konio layers revealed the same supra-granular V1 activation pattern as the one elicited by optogenetics. Taken together, these findings establish a selective koniocellular LGN influence on V1 supra-granular layers, and they indicate comparable capacities of both stimulation methods to isolate thalamo-cortical circuits in the primate brain., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Diffusion magnetic resonance imaging (MRI) allows for the noninvasive in vivo examination of anatomical connections in the human brain, which has an important role in understanding brain function. Validation of this technique is vital, but has proved difficult due to the lack of an adequate gold standard. In this work, the macaque visual system was used as a model as an extensive body of literature of in vivo and postmortem tracer studies has established a detailed understanding of the underlying connections. We performed probabilistic tractography on high angular resolution diffusion imaging data of 2 ex vivo, in vitro macaque brains. Comparisons were made between identified connections at different thresholds of probabilistic connection "strength," and with various tracking optimization strategies previously proposed in the literature, and known connections from the detailed visual system wiring map described by Felleman and Van Essen (1991; FVE91). On average, 74% of connections that were identified by FVE91 were reproduced by performing the most successfully optimized probabilistic diffusion MRI tractography. Further comparison with the results of a more recent tracer study ( Markov et al. 2012) suggests that the fidelity of tractography in estimating the presence or absence of interareal connections may be greater than this., (© The Author 2015. Published by Oxford University Press.)

There is extensive controversy over whether the adult visual cortex is able to reorganize following visual field loss (scotoma) as a result of retinal or cortical lesions. Functional magnetic resonance imaging (fMRI) methods provide a useful tool to study the aggregate receptive field properties and assess the capacity of the human visual cortex to reorganize following injury. However, these methods are prone to biases near the boundaries of the scotoma. Retinotopic changes resembling reorganization have been observed in the early visual cortex of normal subjects when the visual stimulus is masked to simulate retinal or cortical scotomas. It is not known how the receptive fields of higher visual areas, like hV5/MT+, are affected by partial stimulus deprivation. We measured population receptive field (pRF) responses in human area V5/MT+ of 5 healthy participants under full stimulation and compared them with responses obtained from the same area while masking the left superior quadrant of the visual field ("artificial scotoma" or AS). We found that pRF estimations in area hV5/MT+ are nonlinearly affected by the AS. Specifically, pRF centers shift towards the AS, while the pRF amplitude increases and the pRF size decreases near the AS border. The observed pRF changes do not reflect reorganization but reveal important properties of normal visual processing under different test-stimulus conditions., (Copyright © 2015. Published by Elsevier Inc.)

Distributed neural processing likely entails the capability of networks to reconfigure dynamically the directionality and strength of their functional connections. Yet, the neural mechanisms that may allow such dynamic routing of the information flow are not yet fully understood. We investigated the role of gamma band (50-80 Hz) oscillations in transient modulations of communication among neural populations by using measures of direction-specific causal information transfer. We found that the local phase of gamma-band rhythmic activity exerted a stimulus-modulated and spatially-asymmetric directed effect on the firing rate of spatially separated populations within the primary visual cortex. The relationships between gamma phases at different sites (phase shifts) could be described as a stimulus-modulated gamma-band wave propagating along the spatial directions with the largest information transfer. We observed transient stimulus-related changes in the spatial configuration of phases (compatible with changes in direction of gamma wave propagation) accompanied by a relative increase of the amount of information flowing along the instantaneous direction of the gamma wave. These effects were specific to the gamma-band and suggest that the time-varying relationships between gamma phases at different locations mark, and possibly causally mediate, the dynamic reconfiguration of functional connections.

A biologically relevant event is normally the source of multiple, typically correlated, sensory inputs. To optimize perception of the outer world, our brain combines the independent sensory measurements into a coherent estimate. However, if sensory information is not readily available for every pertinent sense, the brain tries to acquire additional information via covert/overt orienting behaviors or uses internal knowledge to modulate sensory sensitivity based on prior expectations. Cross-modal functional modulation of low-level auditory areas due to visual input has been often described; however, less is known about auditory modulations of primary visual cortex. Here, based on some recent evidence, we propose that an unexpected auditory signal could trigger a reflexive overt orienting response towards its source and concomitantly increase the primary visual cortex sensitivity at the locations where the object is expected to enter the visual field. To this end, we propose that three major functionally specific pathways are employed in parallel. A stream orchestrated by the superior colliculus is responsible for the overt orienting behavior, while direct and indirect (via higher-level areas) projections from A1 to V1 respectively enhance spatiotemporal sensitivity and facilitate object detectability.

Neuromodulators determine how neural circuits process information during cognitive states such as wakefulness, attention, learning, and memory. fMRI can provide insight into their function and dynamics, but their exact effect on BOLD responses remains unclear, limiting our ability to interpret the effects of changes in behavioral state using fMRI. Here, we investigated the effects of dopamine (DA) injections on neural responses and haemodynamic signals in macaque primary visual cortex (V1) using fMRI (7T) and intracortical electrophysiology. Aside from DA's involvement in diseases such as Parkinson's and schizophrenia, it also plays a role in visual perception. We mimicked DAergic neuromodulation by systemic injection of L-DOPA and Carbidopa (LDC) or by local application of DA in V1 and found that systemic application of LDC increased the signal-to-noise ratio (SNR) and amplitude of the visually evoked neural responses in V1. However, visually induced BOLD responses decreased, whereas cerebral blood flow (CBF) responses increased. This dissociation of BOLD and CBF suggests that dopamine increases energy metabolism by a disproportionate amount relative to the CBF response, causing the reduced BOLD response. Local application of DA in V1 had no effect on neural activity, suggesting that the dopaminergic effects are mediated by long-range interactions. The combination of BOLD-based and CBF-based fMRI can provide a signature of dopaminergic neuromodulation, indicating that the application of multimodal methods can improve our ability to distinguish sensory processing from neuromodulatory effects., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

The local field potential (LFP) captures different neural processes, including integrative synaptic dynamics that cannot be observed by measuring only the spiking activity of small populations. Therefore, investigating how LFP power is modulated by external stimuli can offer important insights into sensory neural representations. However, gaining such insight requires developing data-driven computational models that can identify and disambiguate the neural contributions to the LFP. Here, we investigated how networks of excitatory and inhibitory integrate-and-fire neurons responding to time-dependent inputs can be used to interpret sensory modulations of LFP spectra. We computed analytically from such models the LFP spectra and the information that they convey about input and used these analytical expressions to fit the model to LFPs recorded in V1 of anesthetized macaques (Macaca mulatta) during the presentation of color movies. Our expressions explain 60%-98% of the variance of the LFP spectrum shape and its dependency upon movie scenes and we achieved this with realistic values for the best-fit parameters. In particular, synaptic best-fit parameters were compatible with experimental measurements and the predictions of firing rates, based only on the fit of LFP data, correlated with the multiunit spike rate recorded from the same location. Moreover, the parameters characterizing the input to the network across different movie scenes correlated with cross-scene changes of several image features. Our findings suggest that analytical descriptions of spiking neuron networks may become a crucial tool for the interpretation of field recordings., (Copyright © 2014 the authors 0270-6474/14/3414589-17$15.00/0.)

Primary visual cortex (V1) was implicated as an important candidate for the site of perceptual suppression in numerous psychophysical and imaging studies. However, neurophysiological results in awake monkeys provided evidence for competition mainly between neurons in areas beyond V1. In particular, only a moderate percentage of neurons in V1 were found to modulate in parallel with perception with magnitude substantially smaller than the physical preference of these neurons. It is yet unclear whether these small modulations are rooted from local circuits in V1 or influenced by higher cognitive states. To address this question we recorded multi-unit spiking activity and local field potentials in area V1 of awake and anesthetized macaque monkeys during the paradigm of binocular flash suppression. We found that a small but significant modulation was present in both the anesthetized and awake states during the flash suppression presentation. Furthermore, the relative amplitudes of the perceptual modulations were not significantly different in the two states. We suggest that these early effects of perceptual suppression might occur locally in V1, in prior processing stages or within early visual cortical areas in the absence of top-down feedback from higher cognitive stages that are suppressed under anesthesia.

Injury to the primary visual cortex (V1) typically leads to loss of conscious vision in the corresponding, homonymous region of the contralateral visual hemifield (scotoma). Several studies suggest that V1 is highly plastic after injury to the visual pathways, whereas others have called this conclusion into question. We used functional magnetic resonance imaging (fMRI) to measure area V1 population receptive field (pRF) properties in five patients with partial or complete quadrantic visual field loss as a result of partial V1+ or optic radiation lesions. Comparisons were made with healthy controls deprived of visual stimulation in one quadrant ["artificial scotoma" (AS)]. We observed no large-scale changes in spared-V1 topography as the V1/V2 border remained stable, and pRF eccentricity versus cortical-distance plots were similar to those of controls. Interestingly, three observations suggest limited reorganization: (i) the distribution of pRF centers in spared-V1 was shifted slightly toward the scotoma border in 2 of 5 patients compared with AS controls; (ii) pRF size in spared-V1 was slightly increased in patients near the scotoma border; and (iii) pRF size in the contralesional hemisphere was slightly increased compared with AS controls. Importantly, pRF measurements yield information about the functional properties of spared-V1 cortex not provided by standard perimetry mapping. In three patients, spared-V1 pRF maps overlapped significantly with dense regions of the perimetric scotoma, suggesting that pRF analysis may help identify visual field locations amenable to rehabilitation. Conversely, in the remaining two patients, spared-V1 pRF maps failed to cover sighted locations in the perimetric map, indicating the existence of V1-bypassing pathways able to mediate useful vision.

fMRI, one of the most important noninvasive brain imaging methods, relies on the blood oxygen level-dependent (BOLD) signal, whose precise underpinnings are still not fully understood. It is a widespread assumption that the components of the hemodynamic response function (HRF) are fixed relative to each other in time, leading most studies as well as analysis tools to focus on trial-averaged responses, thus using or estimating a condition- or location-specific "canonical HRF". In the current study, we examined the nature of the variability of the BOLD response and asked in particular whether the positive BOLD peak is subject to trial-to-trial temporal jitter. Our results show that the positive peak of the stimulus-evoked BOLD signal exhibits a trial-to-trial temporal jitter on the order of seconds. Moreover, the trial-to-trial variability can be exploited to uncover the initial dip in the majority of voxels by pooling trial responses with large peak latencies. Initial dips exposed by this procedure possess higher spatial resolution compared to the positive BOLD signal in the human visual cortex. These findings allow for the reliable observation of fMRI signals that are physiologically closer to neural activity, leading to improvements in both temporal and spatial resolution., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

The visual field is retinotopically represented in early visual areas. It has been suggested that when adult primary visual cortex (V1) is deprived of normal retinal input it is capable of large-scale reorganisation, with neurons inside the lesion projection zone (LPZ) being visually driven by inputs from intact retinal regions. Early functional magnetic resonance imaging (fMRI) studies in humans with macular degeneration (MD) report > 1 cm spread of activity inside the LPZ border, whereas recent results report no shift of the LPZ border. Here, we used fMRI population receptive field measurements to study, for the first time, the visual cortex organisation of one macaque monkey with MD and to compare it with normal controls. Our results showed that the border of the V1 LPZ remained stable, suggesting that the deafferented area V1 zone of the MD animal has limited capacity for reorganisation. Interestingly, the pRF size of non-deafferented V1 voxels increased slightly (~20% on average), although this effect appears weaker than that in previous single-unit recording reports. Area V2 also showed limited reorganisation. Remarkably, area V5/MT of the MD animal showed extensive activation compared to controls stimulated over the part of the visual field that was spared in the MD animal. Furthermore, population receptive field size distributions differed markedly in area V5/MT of the MD animal. Taken together, these results suggest that V5/MT has a higher potential for reorganisation after MD than earlier visual cortex., (© 2013 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.)

We introduce a new method for measuring visual population receptive fields (pRF) with functional magnetic resonance imaging (fMRI). The pRF structure is modeled as a set of weights that can be estimated by solving a linear model that predicts the Blood Oxygen Level-Dependent (BOLD) signal using the stimulus protocol and the canonical hemodynamic response function. This method does not make a priori assumptions about the specific pRF shape and is therefore a useful tool for uncovering the underlying pRF structure at different spatial locations in an unbiased way. We show that our method is more accurate than a previously described method (Dumoulin and Wandell, 2008) which directly fits a 2-dimensional isotropic Gaussian pRF model to predict the fMRI time-series. We demonstrate that direct-fit models do not fully capture the actual pRF shape, and can be prone to pRF center mislocalization when the pRF is located near the border of the stimulus space. A quantitative comparison demonstrates that our method outperforms the direct-fit methods in the pRF center modeling by achieving higher explained variance of the BOLD signal. This was true for direct-fit isotropic Gaussian, anisotropic Gaussian, and difference of isotropic Gaussians model. Importantly, our model is also capable of exploring a variety of pRF properties such as surround suppression, receptive field center elongation, orientation, location and size. Additionally, the proposed method is particularly attractive for monitoring pRF properties in the visual areas of subjects with lesions of the visual pathways, where it is difficult to anticipate what shape the reorganized pRF might take. Finally, the method proposed here is more efficient in computation time than direct-fit methods, which need to search for a set of parameters in an extremely large searching space. Instead, this method uses the pRF topography to constrain the space that needs to be searched for the subsequent modeling., (Copyright © 2013 Elsevier Inc. All rights reserved.)

The six cortical layers have distinct anatomical and physiological properties, like different energy use and different feedforward and feedback connectivity. It is not known if and how layer-specific neural processes are reflected in the fMRI signal. To address this question we used high-resolution fMRI to measure BOLD, CBV, and CBF responses to stimuli that elicit positive and negative BOLD signals in macaque primary visual cortex. We found that regions with positive BOLD responses had parallel increases in CBV and CBF, whereas areas with negative BOLD responses showed a decrease in CBF but an increase in CBV. For positive BOLD responses, CBF and CBV increased in the center of the cortex, but for negative BOLD responses, CBF decreased superficially while CBV increased in the center. Our findings suggest different mechanisms for neurovascular coupling for BOLD increases and decreases, as well as laminar differences in neurovascular coupling., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Local Field Potentials (LFPs) exhibit a broadband spectral structure that is traditionally partitioned into distinct frequency bands which are thought to originate from different types of neural events triggered by different processing pathways. However, the exact frequency boundaries of these processes are not known and, as a result, the frequency bands are often selected based on intuition, previous literature or visual inspection of the data. Here, we address these problems by developing a rigorous method for defining LFP frequency bands and their boundaries. The criterion introduced for determining the boundaries delimiting the bands is to maximize the information about an external correlate carried jointly by all bands in the partition. The method first partitions the LFP frequency range into two bands and then successively increases the number of bands in the partition. We applied the partitioning method to LFPs recorded from primary visual cortex of anaesthetized macaques, and we determined the optimal band partitioning that describes the encoding of naturalistic visual stimuli. The first optimal boundary partitioned the LFP response at 60 Hz into low and high frequencies, which had been previously found to convey independent information about the natural movie correlate. The second optimal boundary divided the high-frequency range at approximately 100 Hz into gamma and high-gamma frequencies, consistent with recent reports that these two bands reflect partly distinct neural processes. A third important boundary was at 25 Hz and it split the LFP range below 50 Hz into a stimulus-informative and a stimulus-independent band., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Mutual information is a principled non-linear measure of dependence between stochastic variables, which is widely used to study the selectivity of neural responses to external stimuli. Here we define and develop a set of novel statistical independence tests based on mutual information, which quantify the significance of neural selectivity to either single features or to multiple, potentially correlated stimulus features like those often present in naturalistic stimuli. If the values of different features are correlated during stimulus presentation, it is difficult to establish if one feature is genuinely encoded by the response, or if it instead appears to be encoded only as a side effect of its correlation with another genuinely represented feature. Our tests provide a way to disambiguate between these two possibilities. We use realistic simulations of neural responses tuned to one or more correlated stimulus features to investigate how limited sampling bias correction procedures affect the statistical power of such independence tests, and we characterize the regimes in which the distribution of information values under the null hypothesis can be approximated by simple distributions (Chi-square or Gaussian). Finally, we apply these tests to experimental data to determine the significance of tuning of the band limited power (BLP) of the gamma [30-100 Hz] frequency range of the primary visual cortical local field potential to multiple correlated features during presentation of naturalistic movies. We show that gamma BLP carries significant, genuine information about orientation, space contrast and time contrast, despite the strong correlations between these features., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Color vision is reserved to only few mammals, such as Old World monkeys and humans. Most Old World monkeys are trichromats. Among them, macaques were shown to exhibit functional domains of color-selectivity, in areas V1 and V2 of the visual cortex. Such color domains have not yet been shown in New World monkeys. In marmosets a sex-linked dichotomy results in dichromatic and trichromatic genotypes, rendering most male marmosets color-blind. Here we used trichromatic female marmosets to examine the intrinsic signal response in V1 and V2 to chromatic and achromatic stimuli, using optical imaging. To activate the subsystems individually, we used spatially homogeneous isoluminant color opponent (red/green, blue/yellow) and hue versus achromatic flicker (red/gray, green/gray, blue/gray, yellow/gray), as well as achromatic luminance flicker. In contrast to previous optical imaging studies in marmosets, we find clearly segregated color domains, similar to those seen in macaques. Red/green and red/gray flicker were found to be the appropriate stimulus for revealing color domains in single-condition maps. Blue/gray and blue/yellow flicker stimuli resulted in faint patch-patterns. A recently described multimodal vessel mapping approach allowed for an accurate alignment of the functional and anatomical datasets. Color domains were tightly colocalized with cytochrome oxidase blobs in V1 and with thin stripes in V2. Thus, our findings are in accord with 2-Deoxy-D-glucose studies performed in V1 of macaques and studies on color representation in V2. Our results suggest a similar organization of early cortical color processing in trichromats of both Old World and New World monkeys.

In contrast to the limited use of functional magnetic resonance imaging (fMRI) in clinical diagnostics, it is currently a mainstay of neuroimaging in clinical and basic brain research. However, its non-invasive use in combination with its high temporal and spatial resolution would make fMRI a perfect diagnostic tool. We are interested in whether a pharmacological challenge imposed on the brain can be reliably traced by the blood oxygen level-dependent (BOLD) signal and possibly further exploited for diagnostics. We have chosen a systemic challenge with lactate and pyruvate to test whether the physiological formation of these monocarboxylic acids contributes to the BOLD signal and can be detected using fMRI. This information is also of interest because lactate levels in the cerebrospinal fluid rise concomitantly with reduced vascular responsiveness of the brain during the progression of Alzheimer disease (AD). We studied the BOLD response after a low-dose lactate challenge and monitored the induced plasma lactate levels in anesthetized non-human primates. We observed reliable lactate-induced BOLD responses, which could be confirmed at population and individual level by their strong correlation with systemic lactate concentrations. Comparable BOLD effects where observed after a slow infusion of pyruvate. We show here that physiological changes in lactate and pyruvate levels are indeed reflected in the BOLD signal, and describe the technical prerequisites to reliably trace a lactate challenge using BOLD-fMRI., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Motion processing regions apart from V5+/MT+ are still relatively poorly understood. Here, we used functional magnetic resonance imaging to perform a detailed functional analysis of the recently described cingulate sulcus visual area (CSv) in the dorsal posterior cingulate cortex. We used distinct types of visual motion stimuli to compare CSv with V5/MT and MST, including a visual pursuit paradigm. Both V5/MT and MST preferred 3D flow over 2D planar motion, responded less yet substantially to random motion, had a strong preference for contralateral versus ipsilateral stimulation, and responded nearly equally to contralateral and to full-field stimuli. In contrast, CSv had a pronounced preference to 2D planar motion over 3D flow, did not respond to random motion, had a weak and nonsignificant lateralization that was significantly smaller than that of MST, and strongly preferred full-field over contralateral stimuli. In addition, CSv had a better capability to integrate eye movements with retinal motion compared with V5/MT and MST. CSv thus differs from V5+/MT+ by its unique preference to full-field, coherent, and planar motion cues. These results place CSv in a good position to process visual cues related to self-induced motion, in particular those associated to eye or lateral head movements.

Little is known about mechanisms mediating a stable perception of the world during pursuit eye movements. Here, we used fMRI to determine to what extent human motion-responsive areas integrate planar retinal motion with nonretinal eye movement signals in order to discard self-induced planar retinal motion and to respond to objective ("real") motion. In contrast to other areas, V3A lacked responses to self-induced planar retinal motion but responded strongly to head-centered motion, even when retinally canceled by pursuit. This indicates a near-complete multimodal integration of visual with nonvisual planar motion signals in V3A. V3A could be mapped selectively and robustly in every single subject on this basis. V6 also reported head-centered planar motion, even when 3D flow was added to it, but was suppressed by retinal planar motion. These findings suggest a dominant contribution of human areas V3A and V6 to head-centered motion perception and to perceptual stability during eye movements., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Short-term memory requires communication between multiple brain regions that collectively mediate the encoding and maintenance of sensory information. It has been suggested that oscillatory synchronization underlies intercortical communication. Yet, whether and how distant cortical areas cooperate during visual memory remains elusive. We examined neural interactions between visual area V4 and the lateral prefrontal cortex using simultaneous local field potential (LFP) recordings and single-unit activity (SUA) in monkeys performing a visual short-term memory task. During the memory period, we observed enhanced between-area phase synchronization in theta frequencies (3-9 Hz) of LFPs together with elevated phase locking of SUA to theta oscillations across regions. In addition, we found that the strength of intercortical locking was predictive of the animals' behavioral performance. This suggests that theta-band synchronization coordinates action potential communication between V4 and prefrontal cortex that may contribute to the maintenance of visual short-term memories.

There is growing evidence that several components of the mass neural activity contributing to the local field potential (LFP) can be partly separated by decomposing the LFP into nonoverlapping frequency bands. Although the blood oxygen level-dependent (BOLD) signal has been found to correlate preferentially with specific frequency bands of the LFP, it is still unclear whether the BOLD signal relates to the activity expressed by each LFP band independently of the others or if, instead, it also reflects specific relationships among different bands. We investigated these issues by recording, simultaneously and with high spatiotemporal resolution, BOLD signal and LFP during spontaneous activity in early visual cortices of anesthetized monkeys (Macaca mulatta). We used information theory to characterize the statistical dependency between BOLD and LFP. We found that the alpha (8-12 Hz), beta (18-30 Hz), and gamma (40-100 Hz) LFP bands were informative about the BOLD signal. In agreement with previous studies, gamma was the most informative band. Both increases and decreases in BOLD signal reliably followed increases and decreases in gamma power. However, both alpha and beta power signals carried information about BOLD that was largely complementary to that carried by gamma power. In particular, the relationship between alpha and gamma power was reflected in the amplitude of the BOLD signal, while the relationship between beta and gamma bands was reflected in the latency of BOLD with respect to significant changes in gamma power. These results lay the basis for identifying contributions of different neural pathways to cortical processing using fMRI.

Saccadic eye movements (SEMs) are the primary means of gating visual information in primates and strongly influence visual perception. The active exploration of the visual environment ("active vision") via SEMs produces suppression during saccades and enhancement afterward (i.e., during fixation) in occipital visual areas. In lateral temporal lobe visual areas, the influence, if any, of eye movements is less well understood, despite the necessity of these areas for forming coherent percepts of objects. The upper bank of the superior temporal sulcus (uSTS) is one such area whose sensitivity to SEMs is unknown. We therefore examined how saccades modulate local field potentials (LFPs) in the uSTS of macaque monkeys while they viewed face and nonface object stimuli. LFP phase concentration increased following fixation onset in the alpha (8-14 Hz), beta (14-30 Hz), and gamma (30-60 Hz) bands and was distinct from the image-evoked response. Furthermore, near-coincident onsets of fixation and image presentation--like those occurring in active vision--led to enhanced responses through greater phase concentration in the same frequency bands. Finally, single-unit activity was modulated by the phase of alpha, beta, and gamma oscillations, suggesting that the observed phase-locking influences spike timing in uSTS. Previous research implicates phase concentration in these frequency bands as a correlate of perceptual performance (Womelsdorf et al., 2006; Bosman et al., 2009). Together, these results demonstrate sensitivity to eye movements in an object-processing region of the brain and represent a plausible neural basis for the enhancement of object processing during active vision.

We have recently used combined electrostimulation, neurophysiology, microinjection and functional magnetic resonance imaging (fMRI) to study the cortical activity patterns elicited during stimulation of cortical afferents in monkeys. We found that stimulation of a site in lateral geniculate nucleus (LGN) increases the fMRI signal in the regions of primary visual cortex receiving input from that site, but suppresses it in the retinotopically matched regions of extrastriate cortex. Intracortical injection experiments showed that such suppression is due to synaptic inhibition. During these experiments, we have consistently observed activation of superior colliculus (SC) following LGN stimulation. Since LGN does not directly project to SC, the current study investigated the origin of SC activation. By examining experimental manipulations inactivating the primary visual cortex, we present here evidence that the robust SC activation, which follows the stimulation of LGN, is due to the activation of corticocollicular pathway., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Many statistical models of coupling between time changes of the band-limited power of neural signals and functional magnetic resonance imaging Blood Oxygenation Level Dependent (BOLD) signal time changes rely on linear convolution. The effect of nonlinear behaviors in single-trial relationships between neural signals and BOLD responses is rarely tested and included in models. Here we investigate whether using a static nonlinearity improves the prediction of single-trial BOLD responses from neural signals. A static nonlinearity is a nonlinear transformation of the convolution of neural responses which is implemented by the same nonlinear function for all time points. We evaluated this approach by applying it to simultaneous recordings of functional magnetic resonance imaging BOLD and band-limited neural signals (Local Field Potentials and Multi Unit Activity) from primary visual cortex of anaesthetized macaques. We found that using a simple polynomial static nonlinearity was sufficient to obtain highly significant improvements of the accuracy of single-trial BOLD prediction over the accuracy obtained with linear convolution. This suggests that static nonlinearities may be a useful tool for a compact and accurate statistical description of neurovascular coupling., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Imaging technologies, such as intrinsic optical imaging (IOI), functional magnetic resonance imaging (fMRI) or multiphoton microscopy provide excellent opportunities to study the relationship between functional signals recorded from a cortical area and the underlying anatomical structure. This, in turn, requires accurate alignment of the recorded functional imaging data with histological datasets from the imaged tissue obtained after the functional experiment. This alignment is complicated by distortions of the tissue which naturally occur during histological treatment, and is particularly difficult to achieve over large cortical areas, such as primate visual areas. We present here a method that uses IOI vessel maps revealed in the time course of the intrinsic signal, in combination with vascular casts and vascular lumen labeling techniques together with a pseudo three dimensional (p3D) reconstruction of the tissue architecture in order to facilitate alignment of IOI data with posthoc histological datasets. We demonstrate that by such a multimodal vessel mapping approach, we are able to constitute a hook in anatomical-functional data alignment that enables the accurate assignment of functional signals over large cortical regions. As an example, we present precise alignments of IOI responses showing orientation selectivity of primate V1 with anatomical sections stained for cytochrome-oxidase-reactivity., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Visual perception is mediated by unique contributions of the numerous brain regions that constitute the visual system. We performed simultaneous recordings of local field potentials (LFPs) and single unit activity (SUA) in areas V4 and lateral prefrontal cortex to characterize their contribution to visual processing. Here, we trained monkeys to identify natural images at different degradation levels in a visual recognition task. We parametrically varied color and structural information of natural images while the animals were performing the task. We show that the visual-evoked potential (VEP) of the LFP in V4 is highly sensitive to color, whereas the VEP in prefrontal cortex predominantly depends on image structure. When examining the relationship between VEP and SUA, we found that stimulus sensitivity for SUA was well predicted by the VEP in PF cortex but not in V4. Our results first reveal a functional specialization in both areas at the level of the LFP and further suggest that the degree to which mesoscopic signals, such as the VEP, are representative of the underlying SUA neural processing may be brain region specific within the context of visual recognition.

A major goal of computational neuroscience is the creation of computer models for cortical areas whose response to sensory stimuli resembles that of cortical areas in vivo in important aspects. It is seldom considered whether the simulated spiking activity is realistic (in a statistical sense) in response to natural stimuli. Because certain statistical properties of spike responses were suggested to facilitate computations in the cortex, acquiring a realistic firing regimen in cortical network models might be a prerequisite for analyzing their computational functions. We present a characterization and comparison of the statistical response properties of the primary visual cortex (V1) in vivo and in silico in response to natural stimuli. We recorded from multiple electrodes in area V1 of 4 macaque monkeys and developed a large state-of-the-art network model for a 5 × 5-mm patch of V1 composed of 35,000 neurons and 3.9 million synapses that integrates previously published anatomical and physiological details. By quantitative comparison of the model response to the "statistical fingerprint" of responses in vivo, we find that our model for a patch of V1 responds to the same movie in a way which matches the statistical structure of the recorded data surprisingly well. The deviation between the firing regimen of the model and the in vivo data are on the same level as deviations among monkeys and sessions. This suggests that, despite strong simplifications and abstractions of cortical network models, they are nevertheless capable of generating realistic spiking activity. To reach a realistic firing state, it was not only necessary to include both N-methyl-d-aspartate and GABA(B) synaptic conductances in our model, but also to markedly increase the strength of excitatory synapses onto inhibitory neurons (>2-fold) in comparison to literature values, hinting at the importance to carefully adjust the effect of inhibition for achieving realistic dynamics in current network models.

The close correlation between energy supply by blood vessels and energy consumption by cellular processes in the brain is the basis of blood flow-related functional imaging techniques. Regional differences in vascular density can be detected using high-resolution functional magnetic resonance imaging. Therefore, inhomogeneities in vascularization might help to identify anatomically distinct areas noninvasively in vivo. It was reported previously that cytochrome oxidase-rich blobs in the striate cortex of squirrel monkeys are characterized by a notably higher vascular density (42% higher than interblob regions). However, blobs have so far never been identified in vivo on the basis of their vascular density. Here, we analyzed blobs of the primary visual cortex of squirrel monkeys and macaques with respect to the relationship between vascularization and cytochrome oxidase activity. By double staining with cytochrome oxidase enzyme histochemistry to define the blobs and collagen type IV immunohistochemistry to quantify the blood vessels, a close correlation between oxidative metabolism and vascularization was confirmed and quantified in detail. The vascular length density in cytochrome oxidase blobs was on average 4.5% higher than in the interblob regions, a difference almost one order of magnitude smaller than previously reported. Thus, the vascular density that is closely associated with local average metabolic activity is a structural equivalent of cerebral metabolism and blood flow. However, the quantitative differences in vascularization between blob and interblob regions are small and below the detectability threshold of the noninvasive hemodynamic imaging methods of today.

We report the results of our experimental and theoretical investigations of the neural response dynamics in primary visual cortex (V1) during naturalistic visual stimulation. We recorded Local Field Potentials (LFPs) and spiking activity from V1 of anaesthetized macaques during binocular presentation of Hollywood color movies. We analyzed these recordings with information theoretic methods, and found that visual information was encoded mainly by two bands of LFP responses: the network fluctuations measured by the phase and power of low-frequency (less than 12 Hz) LFPs; and fast gamma-range (50-100 Hz) oscillations. Both the power and phase of low frequency LFPs carried information largely complementary to that carried by spikes, whereas gamma range oscillations carried information largely redundant to that of spikes. To interpret these results within a quantitative theoretical framework, we then simulated a sparsely connected recurrent network of excitatory and inhibitory neurons receiving slowly varying naturalistic inputs, and we determined how the LFPs generated by the network encoded information about the inputs. We found that this simulated recurrent network reproduced well the experimentally observed dependency of LFP information upon frequency. This network encoded the overall strength of the input into the power of gamma-range oscillations generated by inhibitory-excitatory neural interactions, and encoded slow variations in the input by entraining the network LFP at the corresponding frequency. This dynamical behavior accounted quantitatively for the independent information carried by high and low frequency LFPs, and for the experimentally observed cross-frequency coupling between phase of slow LFPs and the power of gamma LFPs. We also present new results showing that the model's dynamics also accounted for the extra visual information that the low-frequency LFP phase of spike firing carries beyond that carried by spike rates. Overall, our results suggest biological mechanisms by which cortex can multiplex information about naturalistic sensory environments., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Characterizing how different cortical rhythms interact and how their interaction changes with sensory stimulation is important to gather insights into how these rhythms are generated and what sensory function they may play. Concepts from information theory, such as Transfer Entropy (TE), offer principled ways to quantify the amount of causation between different frequency bands of the signal recorded from extracellular electrodes; yet these techniques are hard to apply to real data. To address the above issues, in this study we develop a method to compute fast and reliably the amount of TE from experimental time series of extracellular potentials. The method consisted in adapting efficiently the calculation of TE to analog signals and in providing appropriate sampling bias corrections. We then used this method to quantify the strength and significance of causal interaction between frequency bands of field potentials and spikes recorded from primary visual cortex of anaesthetized macaques, both during spontaneous activity and during binocular presentation of naturalistic color movies. Causal interactions between different frequency bands were prominent when considering the signals at a fine (ms) temporal resolution, and happened with a very short (ms-scale) delay. The interactions were much less prominent and significant at coarser temporal resolutions. At high temporal resolution, we found strong bidirectional causal interactions between gamma-band (40-100 Hz) and slower field potentials when considering signals recorded within a distance of 2 mm. The interactions involving gamma bands signals were stronger during movie presentation than in absence of stimuli, suggesting a strong role of the gamma cycle in processing naturalistic stimuli. Moreover, the phase of gamma oscillations was playing a stronger role than their amplitude in increasing causations with slower field potentials and spikes during stimulation. The dominant direction of causality was mainly found in the direction from MUA or gamma frequency band signals to lower frequency signals, suggesting that hierarchical correlations between lower and higher frequency cortical rhythms are originated by the faster rhythms.

Studies analyzing sensory cortical processing or trying to decode brain activity often rely on a combination of different electrophysiological signals, such as local field potentials (LFPs) and spiking activity. Understanding the relation between these signals and sensory stimuli and between different components of these signals is hence of great interest. We here provide an analysis of LFPs and spiking activity recorded from visual and auditory cortex during stimulation with natural stimuli. In particular, we focus on the time scales on which different components of these signals are informative about the stimulus, and on the dependencies between different components of these signals. Addressing the first question, we find that stimulus information in low frequency bands (<12 Hz) is high, regardless of whether their energy is computed at the scale of milliseconds or seconds. Stimulus information in higher bands (>50 Hz), in contrast, is scale dependent, and is larger when the energy is averaged over several hundreds of milliseconds. Indeed, combined analysis of signal reliability and information revealed that the energy of slow LFP fluctuations is well related to the stimulus even when considering individual or few cycles, while the energy of fast LFP oscillations carries information only when averaged over many cycles. Addressing the second question, we find that stimulus information in different LFP bands, and in different LFP bands and spiking activity, is largely independent regardless of time scale or sensory system. Taken together, these findings suggest that different LFP bands represent dynamic natural stimuli on distinct time scales and together provide a potentially rich source of information for sensory processing or decoding brain activity.

We investigated the use and implementation of a nonlinear methodology for establishing which changes in neurophysiological signals cause changes in the blood oxygenation level-dependent (BOLD) contrast measured in functional magnetic resonance imaging. Unlike previous analytical approaches, which used linear correlation to establish covariations between neural activity and BOLD, we propose a directed information-theoretic measure, the transfer entropy, which can elucidate even highly nonlinear causal relationships between neural activity and BOLD signal. In this study we investigated the practicality of such an analysis given the limited data samples that can be collected experimentally due to the low temporal resolution of BOLD signals. We implemented several algorithms for the estimation of transfer entropy and we tested their effectiveness using simulated local field potentials (LFPs) and BOLD data constructed to match the main statistical properties of real LFP and BOLD signals measured simultaneously in monkey primary visual cortex. We found that using the advanced methods of entropy estimation implemented and described here, a transfer entropy analysis of neurovascular coupling based on experimentally attainable data sets is feasible., (Copyright © 2010 Elsevier Inc. All rights reserved.)

The role of primary visual cortex (area V1) in subjective perception has intrigued students of vision for decades. Specifically, the extent to which the activity of different types of cells (monocular versus binocular) and electrophysiological signals (i.e., local field potentials versus spiking activity) reflect perception is still debated. To address these questions we recorded from area V1 of the macaque using tetrodes during the paradigm of binocular flash suppression, where incongruent images presented dichoptically compete for perceptual dominance. We found that the activity of a minority (20%) of neurons reflect the perceived visual stimulus and these cells exhibited perceptual modulations substantially weaker compared with their sensory modulation induced by congruent stimuli. Importantly, perceptual modulations were found equally often for monocular and binocular cells, demonstrating that perceptual competition in V1 involves mechanisms across both types of neurons. The power of the local field potential (LFP) also showed moderate perceptual modulations with similar percentages of sites showing significant effects across frequency bands (18-22%). The possibility remains that perception may be strongly reflected in more elaborate aspects of activity in V1 circuits (e.g., specific neuronal subtypes) or perceptual states might have a modulatory role on more intricate aspects of V1 firing patterns (e.g., synchronization), not necessarily altering the firing rates of single cells or the LFP power dramatically.

Despite the widespread use of EEGs to measure the large-scale dynamics of the human brain, little is known on how the dynamics of EEGs relates to that of the underlying spike rates of cortical neurons. However, progress was made by recent neurophysiological experiments reporting that EEG delta-band phase and gamma-band amplitude reliably predict some complementary aspects of the time course of spikes of visual cortical neurons. To elucidate the mechanisms behind these findings, here we hypothesize that the EEG delta phase reflects shifts of local cortical excitability arising from slow fluctuations in the network input due to entrainment to sensory stimuli or to fluctuations in ongoing activity, and that the resulting local excitability fluctuations modulate both the spike rate and the engagement of excitatory-inhibitory loops producing gamma-band oscillations. We quantitatively tested these hypotheses by simulating a recurrent network of excitatory and inhibitory neurons stimulated with dynamic inputs presenting temporal regularities similar to that of thalamic responses during naturalistic visual stimulation and during spontaneous activity. The network model reproduced in detail the experimental relationships between spike rate and EEGs, and suggested that the complementariness of the prediction of spike rates obtained from EEG delta phase or gamma amplitude arises from nonlinearities in the engagement of excitatory-inhibitory loops and from temporal modulations in the amplitude of the network input, which respectively limit the predictability of spike rates from gamma amplitude or delta phase alone. The model suggested also ways to improve and extend current algorithms for online prediction of spike rates from EEGs., (Copyright (c) 2009 Elsevier Inc. All rights reserved.)

The processing of color and form is largely segregated within the visual brain. But there is also evidence to suggest that these features are coded in combination early in visual processing. Here, we combined high-resolution functional magnetic resonance imaging (fMRI) together with multivariate pattern classification to examine where in the visual cortex specific color form "conjunctions" are represented. Human subjects viewed visual displays containing colored spiral patterns. The spiral patterns could be red or green, and oriented either clockwise or counterclockwise, leading to 4 possible stimulus configurations. Two additional displays combined 2 of the above single color-form pairings, leading to double conjunctions. We applied linear classifiers to voxel activation patterns obtained while subjects viewed such displays. Our findings not only show that color and form information is coded across retinotopically defined visual areas, but also that the 2 double-conjunction stimuli can be distinguished. The voxels most informative about conjunctions were distinct from those most informative about color or form alone. Our results indicate that conjunctions of form and color may be coded by separate functional units as early as primary visual cortex. The results of this study have implications for theories concerning the segregation and binding of color and form information.

Correlated trial-to-trial variability in the activity of cortical neurons is thought to reflect the functional connectivity of the circuit. Many cortical areas are organized into functional columns, in which neurons are believed to be densely connected and to share common input. Numerous studies report a high degree of correlated variability between nearby cells. We developed chronically implanted multitetrode arrays offering unprecedented recording quality to reexamine this question in the primary visual cortex of awake macaques. We found that even nearby neurons with similar orientation tuning show virtually no correlated variability. Our findings suggest a refinement of current models of cortical microcircuit architecture and function: Either adjacent neurons share only a few percent of their inputs or, alternatively, their activity is actively decorrelated.

Although the electroencephalogram (EEG) is widely used in research and clinical settings, its link to the underlying neural activity during sensory processing remains poorly understood. To investigate this, we made simultaneous recordings of surface EEG, intracortical local field potential, and multiunit activity (MUA) in the alert monkey visual cortex during presentation of natural movies. Using a general linear model, we show that in single trials, EEG power in the gamma band (30-100 Hz) and phase in delta band (2-4 Hz) are significant predictors of the MUA response. Specifically, we found that the MUA response was strongest only when increases in EEG gamma power occurred during the negative-going phase of the delta wave, thus revealing a frequency-band coupling mechanism that can be exploited to infer population spiking activity. This finding may open up a new dimension in the use and interpretation of EEG in normal and pathological conditions.

Bistable perception arises when an ambiguous stimulus under continuous view is perceived as an alternation of two mutually exclusive states. Such a stimulus provides a unique opportunity for understanding the neural basis of visual perception because it dissociates the perception from the visual input. In this paper, we focus on extracting the percept-related features from the local field potential (LFP) in monkey visual cortex for decoding its bistable structure-from-motion (SFM) perception. Our proposed feature extraction approach consists of two stages. First, we estimate and remove from each LFP trial the nonpercept-related stimulus-evoked activity via a local regression method called the locally weighted scatterplot smoothing because of the dissociation between the perception and the stimulus in our experimental paradigm. Second, we use the common spatial patterns approach to design spatial filters based on the residue signals of multiple channels to extract the percept-related features. We exploit a support vector machine (SVM) classifier on the extracted features to decode the reported perception on a single-trial basis. We apply the proposed approach to the multichannel intracortical LFP data collected from the middle temporal (MT) visual cortex in a macaque monkey performing an SFM task. We demonstrate that our approach is effective in extracting the discriminative features of the percept-related activity from LFP and achieves excellent decoding performance. We also find that the enhanced gamma band synchronization and reduced alpha and beta band desynchronization may be the underpinnings of the percept-related activity.

The question of how perception arises from neuronal activity in the visual cortex is of fundamental importance in cognitive neuroscience. To address this question, we adopt a unique experimental paradigm in which bistable structure-from-motion (SFM) stimuli are employed to dissociate the visual input from perception while monitoring the cortical neural activity called local field potential (LFP). Consequently, the stimulus-evoked activity of LFP is not related to perception but the oscillatory induced activity of LFP may be percept-related. In this paper we focus on extracting the percept-related features of the induced activity from LFP in a monkey's visual cortex for decoding its bistable structure-from-motion perception. We first estimate the stimulus-evoked activity via a wavelet-based method and remove it from the single-trial LFP. We then use the common spatial patterns (CSP) approach to design spatial filters to extract the percept-related features from the remaining induced activity. We exploit the linear discriminant analysis (LDA) classifier on the extracted features to decode the reported perception on a single-trial basis. We demonstrate that our approach has excellent performance in estimating the stimulus-evoked activity, outperforming the Wiener filter, least mean square (LMS), and a local regression method called the locally weighted scatterplot smoothing (LOWESS), and that our approach is effective in extracting the discriminative features of the percept-related induced activity from LFP, which leads to excellent decoding performance. We also discover that the enhanced gamma band synchronization and reduced alpha band desynchronization may be the underpinnings of the induced activity.

Brains are restless. We have long known of the existence of a great deal of uninterrupted brain activity that maintains the body in a stable state--from an evolutionary standpoint one of the brain's most ancient tasks. But intrinsic, ongoing activity is not limited to subcortical, life-maintaining structures; cortex, too, is remarkably active even in the absence of a sensory stimulus or a specific behavioral task. This is evident both in its enormous energy consumption at rest and in the large, spontaneous but coherent fluctuations of neural activity that spread across different areas. Not surprisingly, a growing number of electrophysiological and functional magnetic resonance imaging (fMRI) studies are appearing that report on various aspects of the brain's spontaneous activity or "default mode" of operation. One recent study reports results from simultaneously combined electrophysiological and fMRI measurements in the monkey visual cortex (Shmuel, A., Leopold, D.A., 2008. Neuronal correlates of spontaneous fluctuations in fMRI signals in monkey visual cortex: implications for functional connectivity at rest. Hum. Brain Mapp. 29, 751-761). The authors claim to be able to demonstrate correlations between slow fluctuations in blood-oxygen-level-dependent (BOLD) signals and concurrent fluctuations in the underlying, locally measured neuronal activity. They even go on to speculate that the fluctuations display wave-like spatiotemporal patterns across cortex. In the present report, however, we re-analyze the data presented in that study and demonstrate that the measurements were not actually taken during rest. Visual cortex was subject to almost imperceptible but physiologically clearly detectable flicker induced by the visual stimulator. An examination of the power spectral density of the neural responses and the neurovascular impulse response function shows that such imperceptible flicker strongly suppresses the slow oscillations and changes the degree of covariance between neural and vascular signals. In addition, a careful analysis of the spatiotemporal patterns demonstrates that no slow waves of activity exist in visual cortex; instead, the presented wave data reflect differences in signal-to-noise ratio at various cortical sites due to local differences in vascularization. In this report, assuming that the term "spontaneous activity" refers to intrinsic physiological processes at the absence of sensory inputs or motor outputs, we discuss the need for careful selection of experimental protocols and of examining the degree to which the activation of sensory areas might influence the cortical or subcortical processes in other brain regions.

Background: Color and motion serve as the prime examples of segregated processing in the visual brain, giving rise to the question how color-motion conjunctions are represented. This problem is also known as the "binding problem.", Results: Human volunteers viewed visual displays containing colored dots rotating around the center. The dots could be red or green and rotate clockwise or counterclockwise, leading to four possible stimulus displays. Superimposed pairs of such stimuli provided two additional displays, each containing both colors and both directions of motion but differing in their feature conjunctions. We applied multivariate classifiers to voxel-activation patterns obtained while subjects viewed such displays. Our analyses confirm the presence of directional-motion information across visual cortex and provide evidence of hue coding in all early visual areas except V5/MT(+). Within each cortical area, information on color and motion appeared to be coded in distinct sets of voxels. Furthermore, our results demonstrate the explicit representation of feature conjunctions in the primary visual cortex and beyond., Conclusions: The results show that conjunctions can be decoded from spatial activation patterns already in V1, indicating an explicit coding of conjunctions at early stages of visual processing. Our findings raise the possibility that the solution of what has been taken as the prime example of the binding problem engages neural mechanisms as early as V1.

Creating focal lesions in primary visual cortex (V1) provides an opportunity to study the role of extra-geniculo-striate pathways for activating extrastriate visual cortex. Previous studies have shown that more than 95% of neurons in macaque area V2 and V3 stop firing after reversibly cooling V1. However, no studies on long term recovery in areas V2, V3 following permanent V1 lesions have been reported in the macaque. Here we use macaque fMRI to study area V2, V3 activity patterns from 1 to 22 months after lesioning area V1. We find that visually driven BOLD responses persist inside the V1-lesion projection zones (LPZ) of areas V2 and V3, but are reduced in strength by approximately 70%, on average, compared to pre-lesion levels. Monitoring the LPZ activity over time starting one month following the V1 lesion did not reveal systematic changes in BOLD signal amplitude. Surprisingly, the retinotopic organization inside the LPZ of areas V2, V3 remained similar to that of the non-lesioned hemisphere, suggesting that LPZ activation in V2, V3 is not the result of input arising from nearby (non-lesioned) V1 cortex. Electrophysiology recordings of multi-unit activity corroborated the BOLD observations: visually driven multi-unit responses could be elicited inside the V2 LPZ, even when the visual stimulus was entirely contained within the scotoma induced by the V1 lesion. Restricting the stimulus to the intact visual hemi-field produced no significant BOLD modulation inside the V2, V3 LPZs. We conclude that the observed activity patterns are largely mediated by parallel, V1-bypassing, subcortical pathways that can activate areas V2 and V3 in the absence of V1 input. Such pathways may contribute to the behavioral phenomenon of blindsight.

Generalized flash suppression (GFS, Wilke et al. 2003) in which a salient visual stimulus can be rendered invisible despite continuous retinal input has provided a powerful means to study neural processes directly related to perception. However, the mechanisms underlying such perceptual suppression remain poorly understood. Here we asked how reliably the population responses could determine the perceptual states and what the roles of different areas in visual cortex played during suppression. Three monkeys were trained to perform the GFS task. Multi-channel neural activities in visual cortical areas V1, V2 and V4 were simultaneously recorded. Linear regression analysis on the time-frequency distributions of local field potential (LFP) recordings between two perceptual states (visible vs. invisible) showed that the significant power difference existed between the two perceptual states at the beta frequency band of 10-30 Hz. Linear discriminant analysis (LDA) classifiers were implemented to decipher perceptual states. Our results showed that LFP recordings provided significantly better prediction than the chance level, and the beta band signal provided better prediction than the broad band in all the three visual cortical areas. Broad band signal provided more accurate prediction in V4 than in V2 and V1, while the beta band signal provided consistently good predictions in V1, V2 and V4. Furthermore, multi-channel recordings were more informative than single electrode recordings in V1, V2 and V4, while in V1 and V4 the benefit of decoding population activity was significant. Channel-wise correlations limited the benefits of population activity. These results indicated that considerable information was retained in the beta band of the local field potential. The benefits of population activity were explored and the different roles of different visual cortical areas during perceptual suppression were investigated.

Recordings of local field potentials (LFPs) reveal that the sensory cortex displays rhythmic activity and fluctuations over a wide range of frequencies and amplitudes. Yet, the role of this kind of activity in encoding sensory information remains largely unknown. To understand the rules of translation between the structure of sensory stimuli and the fluctuations of cortical responses, we simulated a sparsely connected network of excitatory and inhibitory neurons modeling a local cortical population, and we determined how the LFPs generated by the network encode information about input stimuli. We first considered simple static and periodic stimuli and then naturalistic input stimuli based on electrophysiological recordings from the thalamus of anesthetized monkeys watching natural movie scenes. We found that the simulated network produced stimulus-related LFP changes that were in striking agreement with the LFPs obtained from the primary visual cortex. Moreover, our results demonstrate that the network encoded static input spike rates into gamma-range oscillations generated by inhibitory-excitatory neural interactions and encoded slow dynamic features of the input into slow LFP fluctuations mediated by stimulus-neural interactions. The model cortical network processed dynamic stimuli with naturalistic temporal structure by using low and high response frequencies as independent communication channels, again in agreement with recent reports from visual cortex responses to naturalistic movies. One potential function of this frequency decomposition into independent information channels operated by the cortical network may be that of enhancing the capacity of the cortical column to encode our complex sensory environment.