A spatiotemporal profile of visual system activation revealed by current source density analysis in the awake macaque.

We investigated the spatiotemporal activation pattern, produced by one visual stimulus, across cerebral cortical regions in awake monkeys. Laminar profiles of postsynaptic potentials and action potentials were indexed with current source density (CSD) and multiunit activity profiles respectively. Locally, we found contrasting activation profiles in dorsal and ventral stream areas. The former, like V1 and V2, exhibit a 'feedforward' profile, with excitation beginning at the depth of Lamina 4, followed by activation of the extragranular laminae. The latter often displayed a multilaminar/columnar profile, with initial responses distributed across the laminae and reflecting modulation rather than excitation; CSD components were accompanied by either no changes or by suppression of action potentials. System-wide, response latencies indicated a large dorsal/ventral stream latency advantage, which generalizes across a wide range of methods. This predicts a specific temporal ordering of dorsal and ventral stream components of visual analysis, as well as specific patterns of dorsal-ventral stream interaction. Our findings support a hierarchical model of cortical organization that combines serial and parallel elements. Critical in such a model is the recognition that processing within a location typically entails multiple temporal components or 'waves' of activity, driven by input conveyed over heterogeneous pathways from the retina.

Presumed bilateral occipital neurosarcoidosis. A case report.

A 37-year-old man with a history of sarcoidosis, hypertension, asthma, depression and prior intravenous drug use presented with complaints of difficulty in finding his way around the house, headache, and blurred vision in both eyes. The symptoms had been increasing in severity over the prior several months. Physical examination showed normal visual acuity, pupil reactions, and fundi but severe, circumferential constriction of the visual fields bilaterally. The visual fields enlarged appropriately on increasing the distance from the patient to the tangent screen. Neuroimaging revealed bilateral, occipital meningeal involvement and parenchymal lesions consistent with sarcoidosis. Treatment with oral corticosteroids produced a mild subjective improvement in the patient's symptoms and stabilized the visual fields, without improving them. This case represents an unusual presentation of presumed neurosarcoidosis involving the visual pathways at the level of the occipital lobes.

N-methyl-D-aspartate enhancement of phasic responses in primate neocortex.

In area 17 of the awake macaque, disinhibition by blockade of GABA(A) receptors results in a marked elevation in neuronal excitability, with a particular focus in the supragranular laminae. We examined the possibility that the excitatory supragranular response is N-methyl-D-aspartate (NMDA)-mediated. Laminar activity profiles consisting of flash-evoked field potential, current source density (CSD) and multiunit activity (MUA) measures were obtained during striate cortex penetrations using multicontact electrodes that incorporated single or double microinjection cannulae. Profiles were recorded before and at successive time points after bicuculline induction of disinhibition. Both the noncompetitive NMDA antagonist MK-801 and the competitive antagonist APV reversed bicuculline effects, producing a normal laminar activity profile. NMDA-mediated enhancement of excitatory responses in the supragranular laminae of neocortex is believed to play a role in normal signal processing, as well as in epileptic manifestations.

Effects of wavelength on the timing and laminar distribution of illuminance-evoked activity in macaque V1.

Responses to full-field colored flashes (red, blue, and green) were compared with those to illuminance-matched white flashes in area V1, optic radiations, and the lateral geniculate nucleus of two alert macaques. Laminar profiles of visual evoked potentials (VEPs), current source density, and multiunit activity were obtained using multicontact electrodes capable of sampling from all layers of cortex or lateral geniculate nucleus, simultaneously. In striate cortex, stimulation with colored flash enhanced transmembrane current flow dramatically in both layer 4c and the supragranular laminae. Stimulation with red evoked the largest enhancement in every electrode penetration. The mean peak amplitudes of current sinks evoked by red were 203% and 537% of those evoked by white light in layer 4c and the supragranular laminae, respectively. Color effects in V1 were preceded by an initial epoch of wavelength-insensitive activity. In layer 4c, the red effect reached significance, on average, at 47 ms, or approximately 24 ms after the onset of transmembrane current flow. In the supragranular layers, the red effect reached significance, on average, at 55 ms, or approximately 14 ms after the onset of current flow. Recordings from optic radiations in the white matter below V1 and from lateral geniculate nucleus showed no significant difference in the responses to color and illuminance-matched white light. Enhancement of supragranular current flow with color stimulation increased the contribution of these laminae to the generation of the surface VEP. Comparison of the surface VEP wave forms evoked by white and color stimuli may, therefore, help to differentiate the responses of the granular and supragranular laminae.

Contribution of extrastriate area V4 to the surface-recorded flash VEP in the awake macaque.

This study compared striate and extrastriate contributions to the surface-recorded flash VEP. Laminar visual evoked potential, current source density and multiunit activity profiles were obtained with multicontact electrodes from areas V1 and V4 in three awake macaques. As found earlier, the major striate contribution is to early (N40, P55-80) components. Major contributions to the later (N95, P120, Late Negativity) components arise from V4. Early, afferent-triggered inhibition in V4 also produces a small contribution to N40. Response latencies in V4 vs V1 suggest an input to V4, bypassing V1, emphasizing a parallel processing component of visual system organization.

Subcortical contributions to the surface-recorded flash-VEP in the awake macaque.

Epidural mapping of flash-VEP in awake monkeys revealed a reliable, short latency negativity, N25 (onset: 18-22 msec; peak: 23-27 msec; duration: 15-20 msec), with a broad frontal surface distribution (frontolateral maximum). N25 was dissociable from the electroretinogram (ERG), from cortical VEP and from the high frequency oscillations (wavelets) coextensive with the ERG and with cortical VEP. Depth recordings traced N25 from its surface maximum down to the lateral geniculate nucleus (LGN). Concomitant VEP, current source density (CSD) and multiunit activity (MUA) profiles obtained with multicontact electrodes showed that the peak and later portion of N25 arise primarily from current sinks (associated with MUA increases) that reflect transmembrane current flow attending depolarization of cells in lamina 6, the uppermost lamina, but may also receive contributions from the more ventral LGN laminae. The initial portion of N25 arises from similar processes near the lamina 3/2 border. Wavelets, in contrast, are prominent in VEP, CSD and MUA within LGN, but attenuate rapidly above LGN. LGN laminar and cellular morphology predict volume conduction of N25 over a wide arc lateral and anterior to LGN and roughly horizontal isopotential planes medial and posterior to LGN. Recordings on the brain surface, within LGN, and in the regions surrounding LGN are consistent with these predictions. Possible contributions from other structures and how these results fit with data obtained in humans are considered.

Striate cortical contribution to the surface-recorded pattern-reversal VEP in the alert monkey.

The striate cortical contribution to the surface pattern-reversal visual evoked potential (VEP) was investigated in awake monkeys during performance of a visual fixation task, by examining laminar profiles of VEP, current source density (CSD) and concomitant multiunit activity (MUA) in Area 17, recorded simultaneously at incremental depths using multicontact electrodes. Stimuli were black/white bar gratings centered on the fixation point. The typical surface pattern-reversal VEP over striate cortex consists of a prominent positivity peaking at 50-70 msec (P60), followed by a large negativity peaking at approx. 80 msec (N80), and then by a late broad positivity, peaking between 120 and 150 msec (P125). P60 is often preceded by a small negativity peaking at 45-55 msec (N50), and on rare occasions a small positivity (P40) is also observed. N50 is generated primarily by current sinks in Lamina 4C. P60 arises from large current sources in the supragranular laminae. N80 and P125 appear to be composite waveforms reflecting complex contributions from local activity and from activity occurring outside of the foveal/immediate parafoveal representation in Area 17. The basic physiologic sequence elicited by patterned stimulation is similar to that elicited by diffuse luminance or by electrical stimulation, but is characterized by more prominent supra- and infragranular activation. It is consistent with the cellular and synaptic anatomy of Area 17: initial activation of the thalamorecipient subdivisions of Lamina 4C, followed by activation of mid/upper Lamina 4 and of supra- and infragranular laminae. Our results suggest the possibility of differentiating synaptic stages and cellular processes reflected in the human VEP, based on homologies with simian VEP components.

Laminar analysis of bicuculline-induced epileptiform activity in area 17 of the awake macaque.

We investigated the laminar profile of visually evoked paroxysmal discharge following bicuculline administration in area 17 of the alert macaque. Paroxysmal discharge was focussed in lamina 3, with lesser concomitants in infragranular laminae. There were no marked effects on the flash-evoked laminar activation sequence. The neocortex of the alert macaque studied with the present techniques may provide a model for evaluating basic mechanisms of epilepsy, and for linking these to the macroscopic phenomena seen in humans.