Hamutal Slovin

Physiological aspects of information processing in the basal ganglia of normal and parkinsonian primates

There are two views as to the character of basal-ganglia processing - processing by segregated parallel circuits or by information sharing. To distinguish between these views, we studied the simultaneous activity of neurons in the output stage of the basal ganglia with cross-correlation techniques. The firing of neurons in the globus pallidus of normal monkeys is almost always uncorrelated. However, after dopamine depletion and induction of parkinsonism by treatment with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), oscillatory activity appeared and the firing of many neurons became correlated. We conclude that the normal dopaminergic system supports segregation of the functional subcircuits of the basal ganglia, and that a breakdown of this independent processing is a hallmark of Parkinsons disease.

In-vivo Optical Imaging of Cortical Architecture and Dynamics

A number of new imaging techniques are available to scientists to visualize the functioning brain directly, revealing unprecedented details. These imaging techniques have provided a new level of understanding of the principles underlying cortical development, organization and function. In this chapter we will focus on optical imaging in the living mammalian brain, using two complementary imaging techniques. The first technique is based on intrinsic signals. The second technique is based on voltage-sensitive dyes. Currently, these two optical imaging techniques offer the best spatial and temporal resolution, but also have inherent limitations. We shall provide a few examples of new findings obtained mostly in work done in our laboratory. The focus will be upon the understanding of methodological aspects which in turn should contribute to optimal use of these imaging techniques. General reviews describing earlier work done on simpler preparations have been published elsewhere (Cohen, 1973; Tasaki and Warashina, 1976; Waggoner and Grinvald, 1977; Waggoner, 1979; Salzberg, 1983; Grinvald, 1984; Grinvald et al., 1985; De Weer and Salzberg, 1986; Cohen and Lesher, 1986; Salzberg et al., 1986; Loew, 1987; Orbach, 1987; Blasdel, 1988, 1989; Grinvald et al., 1988; Kamino, 1991; Cinelli and Kauer, 1992; Frostig, 1994).

Dural substitute for long-term imaging of cortical activity in behaving monkeys and its clinical implications.

We present a transparent silicone dural substitute, which we have been using for the last 7 years for imaging cortical dynamics in awake behaving monkeys. This substitute enabled us to record optically for more than a year intrinsic or voltage sensitive dye signals. It is thin and elastic enough to allow microelectrode to pass through without any damage, using full visual control to target the electrode to the desirable recording site. This implant has proved crucial for maintaining the cortex in a good physiological condition and for preserving its optical characteristics that are necessary for optical imaging. We describe the details of the surgical implantation of the silicone dural substitute, the maintenance of the exposed cortex over long periods of time, the cortical reaction to this implant and its possible clinical implications in humans, and the rehabilitation procedure in monkeys.

Non-invasive visualization of cortical columns by fMRI

Functional magnetic resonance imaging can now resolve individual cortical columns, which should provide insights into sensory perception and higher cognitive functions.

Precise Spatiotemporal Patterns among Visual Cortical Areas and Their Relation to Visual Stimulus Processing

Visual processing shows a highly distributed organization in which the presentation of a visual stimulus simultaneously activates neurons in multiple columns across several cortical areas. It has been suggested that precise spatiotemporal activity patterns within and across cortical areas play a key role in higher cognitive, motor, and visual functions. In the visual system, these patterns have been proposed to take part in binding stimulus features into a coherent object, i.e., to be involved in perceptual grouping. Using voltage-sensitive dye imaging (VSDI) in behaving monkeys (Macaca fascicularis, males), we simultaneously measured neural population activity in the primary visual cortex (V1) and extrastriate cortex (V2, V4) at high spatial and temporal resolution. We detected time point population events (PEs) in the VSDI signal of each pixel and found that they reflect transient increased neural activation within local populations by establishing their relation to spiking and local field potential activity. Then, we searched for repeating space and time relations between the detected PEs. We demonstrate the following: (1) spatiotemporal patterns occurring within (horizontal) and across (vertical) early visual areas repeat significantly above chance level; (2) information carried in only a few patterns can be used to reliably discriminate between stimulus categories on a single-trial level; (3) the spatiotemporal patterns yielding high classification performance are characterized by late temporal occurrence and top-down propagation, which are consistent with cortical mechanisms involving perceptual grouping. The pattern characteristics and the robust relation between the patterns and the stimulus categories suggest that spatiotemporal activity patterns play an important role in cortical mechanisms of higher visual processing.

Collinear stimuli induce local and cross-areal coherence in the visual cortex of behaving monkeys.

Background Collinear patterns of local visual stimuli are used to study contextual effects in the visual system. Previous studies have shown that proximal collinear flankers, unlike orthogonal, can enhance the detection of a low contrast central element. However, the direct neural interactions between cortical populations processing the individual flanker elements and the central element are largely unknown. Methodology/Principal Findings Using voltage-sensitive dye imaging (VSDI) we imaged neural population responses in V1 and V2 areas in fixating monkeys while they were presented with collinear or orthogonal arrays of Gabor patches. We then studied the spatio-temporal interactions between neuronal populations processing individual Gabor patches in the two conditions. Time-frequency analysis of the stimulus-evoked VSDI signal showed power increase mainly in low frequencies, i.e., the alpha band (α; 7–14 Hz). Power in the α-band was more discriminative at a single trial level than other neuronal population measures. Importantly, the collinear condition showed an increased intra-areal (V1-V1 and V2-V2) and inter-areal (V1-V2) α-coherence with shorter latencies than the orthogonal condition, both before and after the removal of the stimulus contribution. α-coherence appeared between discrete neural populations processing the individual Gabor patches: the central element and the flankers. Conclusions/Significance Our findings suggest that collinear effects are mediated by synchronization in a distributed network of proximal and distant neuronal populations within and across V1 and V2.

Spatio-temporal characteristics of neurovascular coupling in the anesthetized cat and the awake monkey

Abstract Understanding of the spatio-temporal characteristics of the sensory-evoked cortical blood-volume and oxygenation changes is important from the physiological perspective as well as for the interpretation of results obtained by various neuroimaging techniques, such as optical imaging, PET and f-MRI, and for their improvement. The detailed picture, however, has remained elusive for more than a century. We investigated the blood-volume and oxygenation changes in anesthetized cats and awake monkeys using intrinsic imaging at isosbestic and other wavelengths, laser Doppler, imaging spectroscopy, phosphorescence quenching and fluorescence imaging of activity-dependent responses of intravenously injected extrinsic probes. We found that the onset of blood-volume changes was delayed (>300 ms) with respect to a fast decrease in blood oxygenation. Thus, the blood-volume effects cannot merely explain the “initial dip”. 570-nm measurements and high-resolution imaging (80 ms, 7 μm) of a fluorescent tracer injected into the blood circulation facilitated the resolution of the responses of different microvascular compartments. Preliminary results show that the arterioles led the blood volume increase, rapidly spreading towards the other microvascular compartments. Veins lagged behind. Functional maps of stimulus vs. blank (single condition maps) in a conscious macaque and an anesthetized cat were obtained only during the early deoxygenation phase at 605 nm. At later times or at 570 nm, the vessel artifacts dominated. These results indicated a stronger co-localization of oxygen consumption and electrical activity as compared to the subsequent volume and flow increase, which are not well regulated at the cortical column level.