Daniel Guitton

Frontal lobe lesions in man cause difficulties in suppressing reflexive glances and in generating goal-directed saccades

SummaryThe frontal eye field (FEF) and superior colliculus (SC) are thought to form two parallel systems for generating saccadic eye movements. The SC is thought classically to mediate reflex-like orienting movements. Thus it can be hypothesized that the FEF exerts a higher level control on a visual grasp reflex. To test this hypothesis we have studied the saccades of patients who have had discrete unilateral removals of frontal lobe tissue for the relief of intractable epilepsy. The responses of these patients were compared to those of normal subjects and patients with unilateral temporal lobe removals. Two tasks were used. In the first task the subject was instructed to look in the direction of a visual cue that appeared unexpectedly 12° to the left or right of a central fixation point (FP), in order to identify a patterned target that appeared 200 ms or more later. In the second “anti-saccade” task the subject was required to look not at the location of the cue but in the opposite direction, an equal distance from FP where after 200 ms or more the patterned target appeared. Three major observations have emerged from the present study. (a) Most frontal patients, with lesions involving both the dorsolateral and mesial cortex had long term difficulties in suppressing disallowed glances to visual stimuli that suddenly appeared in peripheral vision. (b) In such patients, saccades that were eventually directed away from the cue and towards the target were nearly always triggered by the appearance of the target itself irrespective of whether or not the “anti-saccade” was preceded by a disallowed glance. Those eye movements away from the cue were only rarely generated spontaneously across the blank screen during the cue-target time interval. (c) The latency of these visually-triggered saccades was very short (80–140 ms) compared to that of the correct saccades (170–200 ms) to the cue when the cue and target were on the same side, thereby suggesting that the structures removed in these patients normally trigger saccades after considerable computations have already been performed. The results support the view that the frontal lobes, particularly the dorsolateral region which contains the FEF and possibly the supplementary motor area contribute to the generation of complex saccadic eye-movement behaviour. More specifically, they appear to aid in suppressing unwanted reflex-like oculomotor activity and in triggering the appropriate volitional movements when the goal for the movement is known but not yet visible.

Stimulation of the superior colliculus in the alert cat

SummaryElectrical stimulation of the cat superior colliculus (SC), in conjunction with the accurate measurement of elicited eye movements and histologically verified electrode positions, has revealed a striking antero-posterior variation in collicular organization. Three zones could be defined in the SC on the basis of eye movement patterns and associated neck muscle EMG activity evoked from the deeper layers. The Anterior zone was coextensive with the central 25 ° of the visual retinotopically coded map contained in the superficial layers. Saccades evoked from this zone were also retinotopically coded, and the latency of EMG activity depended on the position of the eye in the orbit. A similar observation applies to the entire monkey SC. The Intermediate zone was coextensive with the 25 °–70 ° of visual projections. Saccades evoked from this region were “goal-directed” and were associated with invariant, short latency EMG responses. The Posterior zone was found in the extreme caudo-lateral portion of the SC. Eye movements evoked from this zone were centering saccades associated with constant latency EMG activity. The present results in conjunction with previously demonstrated antero-posterior variations in projections to the SC, suggest that the motor strategies controlling gaze shifts toward visual targets vary depending on the location of the target in the visual field.

Control of eye-head coordination during orienting gaze shifts.

Combined eye and head displacements are routinely used to orient the visual axis rapidly (gaze). Humans can use a wide variety of head movement strategies. However, in the cat, comparatively limited eye motility forces a more routine and stereotyped use of head motion. Nevertheless, the same general principles of gaze control may be applicable to humans, rhesus monkeys and cats. The gaze control system can be modeled using a feedback system in which an internally created, instantaneous, gaze motor error signal--equivalent to the distance between the target and the gaze position at that time--is used to drive both eye and head motor circuits. The visual axis is moved until this error equals zero. Recent studies suggest that the superior colliculus of the cat provides brainstem eye and head motor circuits with the gaze motor error signal; such studies have led to speculation that information on ongoing gaze motion is fed back to the superior colliculus. It is still uncertain whether comparable collicular and brainstem neuronal mechanisms control gaze in the monkey.

A Mixed-Signal Multichip Neural Recording Interface With Bandwidth Reduction

We present a multichip structure assembled with a medical-grade stainless-steel microelectrode array intended for neural recordings from multiple channels. The design features a mixed-signal integrated circuit (IC) that handles conditioning, digitization, and time-division multiplexing of neural signals, and a digital IC that provides control, bandwidth reduction, and data communications for telemetry toward a remote host. Bandwidth reduction is achieved through action potential detection and complete capture of waveforms by means of onchip data buffering. The adopted architecture uses high parallelism and low-power building blocks for safety and long-term implantability. Both ICs are fabricated in a CMOS 0.18-mum process and are subsequently mounted on the base of the microelectrode array. The chips are stacked according to a vertical integration approach for better compactness. The presented device integrates 16 channels, and is scalable to hundreds of recording channels. Its performance was validated on a testbench with synthetic neural signals. The proposed interface presents a power consumption of 138 muW per channel, a size of 2.30 mm2, and achieves a bandwidth reduction factor of up to 48 with typical recordings.

Visual, vestibular and voluntary contributions to human head stabilization

SummaryWe have investigated the ability of humans to stabilize their heads in space and assessed the influence of mental set and the relative importance of visual and vestibular cues. Ten normal subjects and 3 patients with bilateral vestibular loss were studied. Subjects were fixed firmly to the chair of a turntable facing a screen on which was projected a target spot. A ‘gunsight’ spot generated by a small projector fixed to the head provided feedback of head position. Four conditions were studied (1) Gunsight (GU): subjects were instructed to stabilize the head in space by superimposing the ‘gunsight’ spot on the fixed target spot while chair position was displaced according to a random pattern with a bandwidth from 0–1 Hz. (2) Imagined gunsight (IGU): identical to condition 1 except that the subject was blindfolded and so had to imagine the target position. (3) Mental arithmetic (MA): subjects did mental arithmetic while the chair was displaced. (4) Visual tracking (VT): subjects were instructed to track the target spot with the ‘gunsight’ spot while the chair was fixed and the target spot driven to follow the chair displacement trajectory used in conditions 1, 2 and 3. In GU normal subjects stabilized their head position extremely well (mean HEAD/CHAIR gain = 0.81). Significant stabilization was present in IGU although the gain (mean gain = 0.61) was reduced compared to GU. There was very little stabilization in MA (mean gain = 0.12). In VT, subjects tracked the target with about the same gain (mean gain = 0.68) as in IGU. By comparison, the vestibular patients could not perform IGU, for which their performance (mean gain = 0.08) was similar to MA (mean gain = 0.06). In GU (mean gain = 0.54), their performance was attributable to visual tracking (mean gain in VT = 0.50). For the frequency bandwidth in which subjects were tested, the results show that: (1) When subjects were distracted by mental arithmetic, the contribution to head stability of the short latency cervico-collic (CCR) and vestibulocollic (VCR) reflexes is negligible. (2) As expected, vision plays an important role in stabilizing the head. (3) Equally important are long latency stabilizing mechanisms whose onset times (140 ms) are shorter, but still comparable to that of vision. (4) The latter mechanisms are of vestibular origin and their influence is under voluntary control so as to permit augmenting head stability compared to what it would be if vision acted alone.

Gaze shifts evoked by stimulation of the superior colliculus in the head-free cat conform to the motor map but also depend on stimulus strength and fixation activity

In our previous paper we demonstrated that electrical microstimulation of the fixation area at the rostral pole of the cat superior colliculus (SC) elicits no gaze movement but, rather, transiently suppresses eye-head gaze saccades. In this paper, we investigated the more caudal region of the SC and its interaction with the fixation area. In the alert head-free cat, supra-threshold stimulation in the anterior portion of the SC but outside the fixation area evoked small saccadic shifts of gaze consisting mainly of an eye movement, the heads contribution being small. Stimulating more posteriorly elicited large gaze saccades consisting of an ocular saccade combined with a rapid head movement. At these latter stimulation sites, craniocentric (goal-directed) eye movements were evoked when the cats head was restrained. The amplitude of eye-head gaze saccades elicited at a particular stimulation site increased with stimulus duration, current strength, and pulse rate, until a constant or “unit” value was reached. The peak velocity of gaze shifts depended on both pulse rate and current strength. The movement direction was not affected by stimulus parameters. The unit gaze vector evoked, in the head-free condition, by stimulating one collicular site was similar to that coded by efferent neurons recorded at that site, thereby indicating a retinotopically coded gaze error representation on the collicular motor map which is not revealed by stimulating the head-fixed animal. Evoked gaze saccades were found to be influenced by fixation behavior. The amplitude of evoked gaze shifts was reduced if stimulation occurred when the hungry animal fixated a food target. Electrical activation of the collicular fixation area was found to mimic well the effects of natural fixation on evoked gaze shifts. Taken together, our results support the view that the overall distribution and level of collicular activity contributes to the encoding of the metrics of gaze saccades. We suggest that the combined levels of activity at the site being stimulated and at the fixation area influence the amplitude of evoked gaze saccades through competition. When stimulation is at low intensities, fixation-related activity reduces the amplitude of evoked gaze saccades. At high activation levels, the site being stimulated dominates and the gaze vector is specified only by that sites collicular output neurons, from which arises the close correspondence between the unit-evoked gaze saccades and the neurally coded gaze vector at that site.

Central Organization and Modeling of Eye‐Head Coordination during Orienting Gaze Shiftsa

An important function of motor control is to coordinate the trajectories of many simultaneously moving and coupled body segments. Perhaps the best understood of such neural systems is the one, reviewed here, that coordinates the eyes and head during a rapid saccadelike orienting movement of the visual axis, referred to as gaze. In this text the main characteristics of normal gaze shifts in alert subjects will be reviewed, and a model control scheme will be proposed which can duplicate the experimental data with several important implications.

The fixation area of the cat superior colliculus: effects of electrical stimulation and direct connection with brainstem omnipause neurons

The superior colliculus has long been recognized as an important structure in the generation of saccadic displacements of the visual axis. Neurons with presaccadic activity encoding saccade vectors are topographically organized and form a “motor map.” Recently, neurons with fixation-related activity have been recorded at the collicular rostral pole, at the area centralis representation or fixation area. Another collicular function which deals with the maintenance of fixation behavior by means of active inhibition of orientation commands was then suggested. We tested that hypothesis as it relates to the suppression of gaze saccades (gaze = eye in space = eye in head + head in space) in the head-free cat by increasing the activity of the fixation cells at the rostral pole with electrical microstimulation. Long stimulation trains applied before gaze saccades delayed their initiation. Short stimuli, delivered during the gaze saccades, transiently interrupted both eye and head components. These results provide further support for a role in fixation behavior for collicular fixation neurons. Brainstem omnipause neurons also exhibit fixation-related activity and have been shown to receive a direct excitatory input from the superior colliculus. To determine whether the collicular projection to omnipause neurons arises from the fixation area, the deep layers of the superior colliculus were electrically stimulated either at the rostral pole including the fixation area or in more caudal regions where stimulation evokes orienting responses. Forty-nine neurons were examined in three cats. 61% of the neurons were found to be orthodromically excited by single-pulse stimulation of the rostral pole, whereas only 29% responded to caudal stimulation. In addition, stimuli delivered to the rostral pole activated, on average, omnipause neurons at shorter latencies and with lower currents than those applied in caudal regions. These results suggest that excitatory inputs to omnipause neurons from the superior colliculus are principally provided by the fixation area, via which the superior colliculus could play a role in suppression of gaze shifts.

The use of system identification techniques in the analysis of oculomotor burst neuron spike train dynamics.

The objective of system identification methods is to construct a mathematical model of a dynamical system in order to describe adequately the input-output relationship observed in that system. Over the past several decades, mathematical models have been employed frequently in the oculomotor field, and their use has contributed greatly to our understanding of how information flows through the implicated brain regions. However, the existing analyses of oculomotor neural discharges have not taken advantage of the power of optimization algorithms that have been developed for system identification purposes. In this article, we employ these techniques to specifically investigate the “burst generator” in the brainstem that drives saccadic eye movements. The discharge characteristics of a specific class of neurons, inhibitory burst neurons (IBNs) that project monosynaptically to ocular motoneurons, are examined. The discharges of IBNs are analyzed using different linear and nonlinear equations that express a neurons firing frequency and history (i.e., the derivative of frequency), in terms of quantities that describe a saccade trajectory, such as eye position, velocity, and acceleration. The variance accounted for by each equation can be compared to choose the optimal model. The methods we present allow optimization across multiple saccade trajectories simultaneously. We are able to investigate objectively how well a specific equation predicts a neurons discharge pattern as well as whether increasing the complexity of a model is justifiable. In addition, we demonstrate that these techniques can be used both to provide an objective estimate of a neurons dynamic latency and to test whether a neurons initial firing rate (expressed as an initial condition) is a function of a quantity describing a saccade trajectory (such as initial eye position).

Superior colliculus encodes distance to target, not saccade amplitude, in multi-step gaze shifts

The superior colliculus (SC) is important for generating coordinated eye–head gaze saccades. Its deeper layers contain a retinotopically organized motor map in which each site is thought to encode a specific gaze saccade vector. Here we show that this fundamental assumption in current models of collicular function does not hold true during horizontal multi-step gaze shifts in darkness that are directed to a goal and composed of a sequence of gaze saccades separated by periods of steady fixation. At the start of a multi-step gaze shift in cats, neural activity on the SCs map was located caudally to encode the overall amplitude of the gaze displacement, not the first saccade in the sequence. As the gaze shift progressed, the locus of activity moved to encode the error between the goal and the current gaze position. Contrary to common belief, the locus of activity never encoded gaze saccade amplitude, except for the last saccade in the sequence.