Alexander Maier

Neural basis of global resting-state fMRI activity

Functional MRI (fMRI) has uncovered widespread hemodynamic fluctuations in the brain during rest. Recent electroencephalographic work in humans and microelectrode recordings in anesthetized monkeys have shown this activity to be correlated with slow changes in neural activity. Here we report that the spontaneous fluctuations in the local field potential (LFP) measured from a single cortical site in monkeys at rest exhibit widespread, positive correlations with fMRI signals over nearly the entire cerebral cortex. This correlation was especially consistent in a band of upper gamma-range frequencies (40–80 Hz), for which the hemodynamic signal lagged the neural signal by 6–8 s. A strong, positive correlation was also observed in a band of lower frequencies (2–15 Hz), albeit with a lag closer to zero. The global pattern of correlation with spontaneous fMRI fluctuations was similar whether the LFP signal was measured in occipital, parietal, or frontal electrodes. This coupling was, however, dependent on the monkeys behavioral state, being stronger and anticipatory when the animals’ eyes were closed. These results indicate that the often discarded global component of fMRI fluctuations measured during the resting state is tightly coupled with underlying neural activity.

Stable perception of visually ambiguous patterns

During the viewing of certain patterns, widely known as ambiguous or puzzle figures, perception lapses into a sequence of spontaneous alternations, switching every few seconds between two or more visual interpretations of the stimulus. Although their nature and origin remain topics of debate, these stochastic switches are generally thought to be the automatic and inevitable consequence of viewing a pattern without a unique solution. We report here that in humans such perceptual alternations can be slowed, and even brought to a standstill, if the visual stimulus is periodically removed from view. We also show, with a visual illusion, that this stabilizing effect hinges on perceptual disappearance rather than on actual removal of the stimulus. These findings indicate that uninterrupted subjective perception of an ambiguous pattern is required for the initiation of the brain-state changes underlying multistable vision.

Divergence of fMRI and neural signals in V1 during perceptual suppression in the awake monkey

The role of primary visual cortex (V1) in determining the contents of perception is controversial. Human functional magnetic resonance imaging (fMRI) studies of perceptual suppression have revealed a robust drop in V1 activity when a stimulus is subjectively invisible. In contrast, monkey single-unit recordings have failed to demonstrate such perception-locked changes in V1. To investigate the basis of this discrepancy, we measured both the blood oxygen level–dependent (BOLD) response and several electrophysiological signals in two behaving monkeys. We found that all signals were in good agreement during conventional stimulus presentation, showing strong visual modulation to presentation and removal of a stimulus. During perceptual suppression, however, only the BOLD response and the low-frequency local field potential (LFP) power showed decreases, whereas the spiking and high-frequency LFP power were unaffected. These results demonstrate that the coupling between the BOLD and electrophysiological signals in V1 is context dependent, with a marked dissociation occurring during perceptual suppression.

Layer-Specific Entrainment of Gamma-Band Neural Activity by the Alpha Rhythm in Monkey Visual Cortex

Although the mammalian neocortex has a clear laminar organization, layer-specific neuronal computations remain to be uncovered. Several studies suggest that gamma band activity in primary visual cortex (V1) is produced in granular and superficial layers and is associated with the processing of visual input. Oscillatory alpha band activity in deeper layers has been proposed to modulate neuronal excitability associated with changes in arousal and cognitive factors. To investigate the layer-specific interplay between these two phenomena, we characterized the coupling between alpha and gamma band activity of the local field potential in V1 of the awake macaque. Using multicontact laminar electrodes to measure spontaneous signals simultaneously from all layers of V1, we found a robust coupling between alpha phase in the deeper layers and gamma amplitude in granular and superficial layers. Moreover, the power in the two frequency bands was anticorrelated. Taken together, these findings demonstrate robust interlaminar cross-frequency coupling in the visual cortex, supporting the view that neuronal activity in the alpha frequency range phasically modulates processing in the cortical microcircuit in a top-down manner.

Distinct Superficial and Deep Laminar Domains of Activity in the Visual Cortex during Rest and Stimulation

Spatial patterns of spontaneous neural activity at rest have previously been associated with specific networks in the brain, including those pertaining to the functional architecture of the primary visual cortex (V1). However, despite the prominent anatomical differences between cortical layers, little is known about the laminar pattern of spontaneous activity in V1. We address this topic by investigating the amplitude and coherence of ongoing local field potential (LFP) signals measured from different layers in V1 of macaque monkeys during rest and upon presentation of a visual stimulus. We used a linear microelectrode array to measure LFP signals at multiple, evenly spaced positions throughout the cortical thickness. Analyzing both the mean LFP amplitudes and between-contact LFP coherences, we identified two distinct zones of activity, roughly corresponding to superficial and deep layers, divided by a sharp transition near the bottom of layer 4. The LFP signals within each laminar zone were highly coherent, whereas those between zones were not. This functional compartmentalization was found not only during rest, but also when the receptive field was stimulated during a visual task. These results demonstrate the existence of distinct superficial and deep functional domains of coherent LFP activity in V1 that may reflect the intrinsic interplay of V1 microcircuitry with cortical and subcortical targets, respectively.

Infragranular sources of sustained local field potential responses in macaque primary visual cortex.

A local field potential (LFP) response can be measured throughout the visual cortex in response to the abrupt appearance of a visual stimulus. Averaging LFP responses to many stimulus presentations isolates transient, phase-locked components of the response that are consistent from trial to trial. However, stimulus responses are also composed of sustained components, which differ in their phase from trial to trial and therefore must be evaluated using other methods, such as computing the power of the response of each trial before averaging. Here, we investigate the basis of phase-locked and non-phase-locked LFP responses in the primary visual cortex of the macaque monkey using a novel variant of current source density (CSD) analysis. We applied a linear array of electrode contacts spanning the thickness of the cortex to measure the LFP and compute band-limited CSD power to identify the laminar sites of persistent current exchange that may be the basis of sustained visual LFP responses. In agreement with previous studies, we found a short-latency phase-locked current sink, thought to correspond to thalamocortical input to layer 4C. In addition, we found a prominent non-phase-locked component of the CSD that persisted as long as the stimulus was physically present. The latter was relatively broadband, lasted throughout the stimulus presentation, and was centered ∼500 μm deeper than the initial current sink. These findings demonstrate a fundamental difference in the neural mechanisms underlying the initial and sustained processing of simple visual stimuli in the V1 microcircuit.

Context-dependent perceptual modulation of single neurons in primate visual cortex

Some neurons in the visual cortex alter their spiking rate according to the perceptual interpretation of an observed stimulus, rather than its physical structure alone. Experiments in monkeys have suggested that, although the proportion of neurons showing this effect differs greatly between cortical areas, this proportion remains similar across different stimuli. These findings have raised the intriguing questions of whether the same neurons always participate in the disambiguation of sensory patterns and whether such neurons might represent a special class of cortical cells that relay perceptual signals to higher cortical areas. Here we explore this question by measuring activity in the middle temporal cortex of monkeys and asking to what degree the percept-related responses of individual neurons depend upon the specific sensory input. In contrast to our expectations, we found that even small differences in the stimuli led to significant changes in the signaling of the perceptual state by single neurons. We conclude that nearly all feature-responsive neurons in this area, rather than a select subset, can contribute to the resolution of sensory conflict, and that the role of individual cells in signaling the perceptual outcome is tightly linked to the fine details of the stimuli involved.

Microcircuitry of Agranular Frontal Cortex: Testing the Generality of the Canonical Cortical Microcircuit

We investigated whether a frontal area that lacks granular layer IV, supplementary eye field, exhibits features of laminar circuitry similar to those observed in primary sensory areas. We report, for the first time, visually evoked local field potentials (LFPs) and spiking activity recorded simultaneously across all layers of agranular frontal cortex using linear electrode arrays. We calculated current source density from the LFPs and compared the laminar organization of evolving sinks to those reported in sensory areas. Simultaneous, transient synaptic current sinks appeared first in layers III and V followed by more prolonged current sinks in layers I/II and VI. We also found no variation of single- or multi-unit visual response latency across layers, and putative pyramidal neurons and interneurons displayed similar response latencies. Many units exhibited pronounced discharge suppression that was strongest in superficial relative to deep layers. Maximum discharge suppression also occurred later in superficial than in deep layers. These results are discussed in the context of the canonical cortical microcircuit model originally formulated to describe early sensory cortex. The data indicate that agranular cortex resembles sensory areas in certain respects, but the cortical microcircuit is modified in nontrivial ways.

Spontaneous Neural Dynamics and Multi-scale Network Organization.

Spontaneous neural activity has historically been viewed as task-irrelevant noise that should be controlled for via experimental design, and removed through data analysis. However, electrophysiology and functional MRI studies of spontaneous activity patterns, which have greatly increased in number over the past decade, have revealed a close correspondence between these intrinsic patterns and the structural network architecture of functional brain circuits. In particular, by analyzing the large-scale covariation of spontaneous hemodynamics, researchers are able to reliably identify functional networks in the human brain. Subsequent work has sought to identify the corresponding neural signatures via electrophysiological measurements, as this would elucidate the neural origin of spontaneous hemodynamics and would reveal the temporal dynamics of these processes across slower and faster timescales. Here we survey common approaches to quantifying spontaneous neural activity, reviewing their empirical success, and their correspondence with the findings of neuroimaging. We emphasize invasive electrophysiological measurements, which are amenable to amplitude- and phase-based analyses, and which can report variations in connectivity with high spatiotemporal precision. After summarizing key findings from the human brain, we survey work in animal models that display similar multi-scale properties. We highlight that, across many spatiotemporal scales, the covariance structure of spontaneous neural activity reflects structural properties of neural networks and dynamically tracks their functional repertoire.

Receptive field focus of visual area V4 neurons determines responses to illusory surfaces

Significance Visual information is often fragmented, such as when objects block each other from view, and our brain must actively deduce missing parts of an image to perceive key features of the world. This study asks whether neurons in cortical area V4 can infer the presence of an object’s surface when visual clues are limited. Indeed, our experiments reveal that certain V4 neurons enhance their responses to an array of stimuli only when they are configured to give rise to an illusory surface. Intriguingly, this effect exhibited unexpected spatial precision relative to the inducing components of the illusion. These findings provide important clues about how the brain overcomes a fundamental challenge of vision. Illusory figures demonstrate the visual system’s ability to infer surfaces under conditions of fragmented sensory input. To investigate the role of midlevel visual area V4 in visual surface completion, we used multielectrode arrays to measure spiking responses to two types of visual stimuli: Kanizsa patterns that induce the perception of an illusory surface and physically similar control stimuli that do not. Neurons in V4 exhibited stronger and sometimes rhythmic spiking responses for the illusion-promoting configurations compared with controls. Moreover, this elevated response depended on the precise alignment of the neuron’s peak visual field sensitivity (receptive field focus) with the illusory surface itself. Neurons whose receptive field focus was over adjacent inducing elements, less than 1.5° away, did not show response enhancement to the illusion. Neither receptive field sizes nor fixational eye movements could account for this effect, which was present in both single-unit signals and multiunit activity. These results suggest that the active perceptual completion of surfaces and shapes, which is a fundamental problem in natural visual experience, draws upon the selective enhancement of activity within a distinct subpopulation of neurons in cortical area V4.