Effects of Stimulus Size and Contrast on the Initial Primary Visual Cortical Response in Humans.

Decades of intracranial electrophysiological investigation into the primary visual cortex (V1) have produced many fundamental insights into the computations carried out in low-level visual circuits of the brain. Some of the most important work has been simply concerned with the precise measurement of neural response variations as a function of elementary stimulus attributes such as contrast and size. Surprisingly, such simple but fundamental characterization of V1 responses has not been carried out in human electrophysiology. Here we report such a detailed characterization for the initial "C1" component of the scalp-recorded visual evoked potential (VEP). The C1 is known to be dominantly generated by initial afferent activation in V1, but is difficult to record reliably due to interindividual anatomical variability. We used pattern-pulse multifocal VEP mapping to identify a stimulus position that activates the left lower calcarine bank in each individual, and afterwards measured robust negative C1s over posterior midline scalp to gratings presented sequentially at that location. We found clear and systematic increases in C1 peak amplitude and decreases in peak latency with increasing size as well as with increasing contrast. With a sample of 15 subjects and ~180 trials per condition, reliable C1 amplitudes of -0.46 µV were evoked at as low a contrast as 3.13% and as large as -4.82 µV at 100% contrast, using stimuli of 3.33° diameter. A practical implication is that by placing sufficiently-sized stimuli to target favorable calcarine cortical loci, robust V1 responses can be measured at contrasts close to perceptual thresholds, which could greatly facilitate principled studies of early visual perception and attention.

Electrophysiological indices of surround suppression in humans.

Surround suppression is a well-known example of contextual interaction in visual cortical neurophysiology, whereby the neural response to a stimulus presented within a neuron's classical receptive field is suppressed by surrounding stimuli. Human psychophysical reports present an obvious analog to the effects seen at the single-neuron level: stimuli are perceived as lower-contrast when embedded in a surround. Here we report on a visual paradigm that provides relatively direct, straightforward indices of surround suppression in human electrophysiology, enabling us to reproduce several well-known neurophysiological and psychophysical effects, and to conduct new analyses of temporal trends and retinal location effects. Steady-state visual evoked potentials (SSVEP) elicited by flickering "foreground" stimuli were measured in the context of various static surround patterns. Early visual cortex geometry and retinotopic organization were exploited to enhance SSVEP amplitude. The foreground response was strongly suppressed as a monotonic function of surround contrast. Furthermore, suppression was stronger for surrounds of matching orientation than orthogonally-oriented ones, and stronger at peripheral than foveal locations. These patterns were reproduced in psychophysical reports of perceived contrast, and peripheral electrophysiological suppression effects correlated with psychophysical effects across subjects. Temporal analysis of SSVEP amplitude revealed short-term contrast adaptation effects that caused the foreground signal to either fall or grow over time, depending on the relative contrast of the surround, consistent with stronger adaptation of the suppressive drive. This electrophysiology paradigm has clinical potential in indexing not just visual deficits but possibly gain control deficits expressed more widely in the disordered brain.

The cruciform model of striate generation of the early VEP, re-illustrated, not revoked: a reply to Ales et al. (2013).

Here we summarize the points raised in our dialog with Ales and colleagues on the cortical generators of the early visual evoked potential (VEP), and offer observations on the results of additional simulations that were run in response to our original comment. For small stimuli placed at locations in the upper and lower visual field for which the human VEP has been well characterized, simulated scalp projections of each of the visual areas V1, V2 and V3 invert in polarity. However, the empirically measured, earliest VEP component, "C1," matches the simulated V1 generators in terms of polarity and topography, but not the simulated V2 and V3 generators. We thus conclude that, 1) consistent with the title of Ales et al. (2010a), polarity inversion on its own is not a sufficient criterion for inferring neuroelectric sources in primary visual cortex; but 2) inconsistent with additional claims made in Ales et al. (2010a), the simulated topographies provide additional evidence for - not against - the tenet that the C1 component is generated in V1.

Microinjectrode System for Combined Drug Infusion and Electrophysiology.

This microinjectrode system is designed for drug infusion, electrophysiology, and delivery and retrieval of experimental probes, such as microelectrodes and nanosensors, optimized for repeated use in awake, behaving animals. The microinjectrode system can be configured for multiple purposes: (1) simple arrangement of the cannula for placement of an experimental probe that would otherwise be too fragile to penetrate the dura mater, (2) microfluidic infusion of a drug, either independently or coupled to a cannula containing an experimental probe (i.e., microelectrode, nanosensor). In this protocol we explain the step by step construction of the microinjectrode, its coupling to microfluidic components, and the protocol for use of the system in vivo. The microfluidic components of this system allow for delivery of volumes on the nanoliter scale, with minimal penetration damage. Drug infusion can be performed independently or simultaneously with experimental probes such as microelectrodes or nanosensors in an awake, behaving animal. Applications of this system range from measuring the effects of a drug on cortical electrical activity and behavior, to understanding the function of a specific region of cortex in the context of behavioral performance based on probe or nanosensor measurements. To demonstrate some of the capabilities of this system, we present an example of muscimol infusion for reversible inactivation of the frontal eye field (FEF) in rhesus macaque during a working memory task.

Altered dynamics of visual contextual interactions in Parkinson's disease.

Over the last decades, psychophysical and electrophysiological studies in patients and animal models of Parkinson's disease (PD), have consistently revealed a number of visual abnormalities. In particular, specific alterations of contrast sensitivity curves, electroretinogram (ERG), and visual-evoked potentials (VEP), have been attributed to dopaminergic retinal depletion. However, fundamental mechanisms of cortical visual processing, such as normalization or "gain control" computations, have not yet been examined in PD patients. Here, we measured electrophysiological indices of gain control in both space (surround suppression) and time (sensory adaptation) in PD patients based on steady-state VEP (ssVEP). Compared with controls, patients exhibited a significantly higher initial ssVEP amplitude that quickly decayed over time, and greater relative suppression of ssVEP amplitude as a function of surrounding stimulus contrast. Meanwhile, EEG frequency spectra were broadly elevated in patients relative to controls. Thus, contrary to what might be expected given the reduced contrast sensitivity often reported in PD, visual neural responses are not weaker; rather, they are initially larger but undergo an exaggerated degree of spatial and temporal gain control and are embedded within a greater background noise level. These differences may reflect cortical mechanisms that compensate for dysfunctional center-surround interactions at the retinal level.

Exploiting individual primary visual cortex geometry to boost steady state visual evoked potentials.

OBJECTIVE: The steady-state visual evoked potential (SSVEP) is an electroencephalographic response to flickering stimuli generated partly in primary visual area V1. The typical 'cruciform' geometry and retinotopic organization of V1 is such that certain neighboring visual regions project to neighboring cortical regions of opposite orientation. Here, we explored ways to exploit this organization in order to boost scalp SSVEP amplitude via oscillatory summation. APPROACH: We manipulated flicker-phase offsets among angular segments of a large annular stimulus in three ways, and compared the resultant SSVEP power to a conventional condition with no temporal phase offsets. (1) We divided the annulus into standard octants for all subjects, and flickered upper horizontal octants with opposite temporal phase to the lower horizontal ones, and left vertical octants opposite to the right vertical ones; (2) we individually adjusted the boundaries between the eight contiguous segments of the standard octants condition to coincide with cruciform-consistent, early-latency topographical shifts in pattern-pulse multifocal visual-evoked potentials (PPMVEP) derived for each of 32 equal-sized segments; (3) we assigned phase offsets to stimulus segments following an automatic algorithm based on the relative amplitudes of vertically- and horizontally-oriented PPMVEP components. MAIN RESULTS: The three flicker-phase manipulations resulted in a significant enhancement of normalized SSVEP power of (1) 202%, (2) 383%, and (3) 300%, respectively. SIGNIFICANCE: We have thus demonstrated a means to obtain more reliable measures of visual evoked activity purely through consideration of cortical geometry. This principle stands to impact both basic and clinical research using SSVEPs.