Sergei Kurkin

Relating Neuronal Firing Patterns to Functional Differentiation of Cerebral Cortex

It has been empirically established that the cerebral cortical areas defined by Brodmann one hundred years ago solely on the basis of cellular organization are closely correlated to their function, such as sensation, association, and motion. Cytoarchitectonically distinct cortical areas have different densities and types of neurons. Thus, signaling patterns may also vary among cytoarchitectonically unique cortical areas. To examine how neuronal signaling patterns are related to innate cortical functions, we detected intrinsic features of cortical firing by devising a metric that efficiently isolates non-Poisson irregular characteristics, independent of spike rate fluctuations that are caused extrinsically by ever-changing behavioral conditions. Using the new metric, we analyzed spike trains from over 1,000 neurons in 15 cortical areas sampled by eight independent neurophysiological laboratories. Analysis of firing-pattern dissimilarities across cortical areas revealed a gradient of firing regularity that corresponded closely to the functional category of the cortical area; neuronal spiking patterns are regular in motor areas, random in the visual areas, and bursty in the prefrontal area. Thus, signaling patterns may play an important role in function-specific cerebral cortical computation.

Coding of smooth eye movements in three-dimensional space by frontal cortex

Through the development of a high-acuity fovea, primates with frontal eyes have acquired the ability to use binocular eye movements to track small objects moving in space. The smooth-pursuit system moves both eyes in the same direction to track movement in the frontal plane (frontal pursuit), whereas the vergence system moves left and right eyes in opposite directions to track targets moving towards or away from the observer (vergence tracking). In the cerebral cortex and brainstem, signals related to vergence eye movements—and the retinal disparity and blur signals that elicit them—are coded independently of signals related to frontal pursuit. Here we show that these types of signal are represented in a completely different way in the smooth-pursuit region of the frontal eye fields. Neurons of the frontal eye field modulate strongly during both frontal pursuit and vergence tracking, which results in three-dimensional cartesian representations of eye movements. We propose that the brain creates this distinctly different intermediate representation to allow these neurons to function as part of a system that enables primates to track and manipulate objects moving in three-dimensional space.

Neuronal Activity in the Caudal Frontal Eye Fields of Monkeys during Memory-Based Smooth Pursuit Eye Movements: Comparison with the Supplementary Eye Fields

Recently, we examined the neuronal substrate of predictive pursuit during memory-based smooth pursuit and found that supplementary eye fields (SEFs) contain signals coding assessment and memory of visual motion direction, decision not-to-pursue (“no-go”), and preparation for pursuit. To determine whether these signals were unique to the SEF, we examined the discharge of 185 task-related neurons in the caudal frontal eye fields (FEFs) in 2 macaques. Visual motion memory and no-go signals were also present in the caudal FEF but compared with those in the SEF, the percentage of neurons coding these signals was significantly lower. In particular, unlike SEF neurons, directional visual motion responses of caudal FEF neurons decayed exponentially. In contrast, the percentage of neurons coding directional pursuit eye movements was significantly higher in the caudal FEF than in the SEF. Unlike SEF inactivation, muscimol injection into the caudal FEF did not induce direction errors or no-go errors but decreased eye velocity during pursuit causing an inability to compensate for the response delays during sinusoidal pursuit. These results indicate significant differences between the 2 regions in the signals represented and in the effects of chemical inactivation suggesting that the caudal FEF is primarily involved in generating motor commands for smooth-pursuit eye movements.

Directional asymmetry in smooth ocular tracking in the presence of visual background in young and adult primates

The smooth pursuit system moves the eyes in space accurately while compensating for visual inputs from the moving background and/or vestibular inputs during head movements. To understand the mechanisms underlying such interactions, we examined the influence of a stationary textured visual background on smooth pursuit tracking and compared the results in young and adult humans and monkeys. Six humans (three children, three adults) and six macaque monkeys (five young, one adult) were used. Human eye movements were recorded using infrared oculography and evoked by a sinusoidally moving target presented on a computer monitor. Scleral search coils were used for monkeys while they tracked a target presented on a tangent screen. The target moved in a sinusoidal or trapezoidal fashion with or without whole body rotation in the same plane. Two kinds of backgrounds, homogeneous and stationary textured, were used. Eye velocity gains (eye velocity/target velocity) were calculated in each condition to compare the influence of the textured background. Children showed asymmetric eye movements during vertical pursuit across the textured (but not the homogeneous) background; upward pursuit was severely impaired, and consisted mostly of catch-up saccades. In contrast, adults showed no asymmetry during pursuit across the different backgrounds. Monkeys behaved similarly; only slight effects were observed with the textured background in a mature monkey, whereas upward pursuit was severely impaired in young monkeys. In addition, VOR cancellation was severely impaired during upward eye and head movements, resulting in residual downward VOR in young monkeys. From these results, we conclude that the directional asymmetry observed in young primates may reflect a different neural organization of the vertical, particularly upward, pursuit system in the face of conflicting visual and vestibular inputs that can be associated with pursuit eye movements. Apparently, proper compensation matures later.

Neurons in the Caudal Frontal Eye Fields of Monkeys Signal Three‐Dimensional Tracking

To maintain optimal clarity of objects moving in three dimensions, precise coordination of binocular eye movements is required in frontal‐eyed primates. Caudal parts of the frontal eye fields (FEFs) contain smooth pursuit neurons and the discharge of the majority of them is related to vergence eye movements as well. However, whether or not those pursuit neurons carry true binocular signals has not been tested critically. Using dichoptic stimuli that dissociate horizontal movements of the left and right eyes, we found that all pursuit‐related, FEF neurons tested carried binocular signals.

Predictive signals in the pursuit area of the monkey frontal eye fields.

In order to pursue a moving target with our eyes, visual motion-signals are converted into eye movement commands. Because of delays in processing visual information, prediction is necessary to compensate for those response-delays and maintain target images on the foveae. Previous studies showed that the majority of FEF pursuit neurons receive visual signals related to actual and predicted target motion. However, in those studies, discharge related to the memory of visual motion could not be separated from that related to prediction. To distinguish the two, while fixating a stationary spot, monkeys were required to memorize the direction of random dot motion (cue-1). After a delay (delay-1), a second cue (cue-2) instructed the monkeys to prepare either pursuit in the memorized direction or to maintain fixation. After a second delay (delay-2), the monkeys selected the correct response. In virtually all tested neurons that showed a visual motion-response to cue-1, the response was not maintained during the delay-1. The majority of responsive neurons were modulated during cue-2 and delay-2. Changing the delay-2 duration also changed the duration of discharge modulation, suggesting that delay-2 modulation was predictive. These results suggest that activity related to visual motion-memory was not conveyed by the discharge of caudal FEF pursuit neurons.

Vergence eye movement signals in the cerebellar dorsal vermis.

We examined simple-spike activity of Purkinje cells (P-cells) that responded during a search task which required both vergence- and frontal-pursuit. Of a total of 100 responding P-cells, 16% discharged only for frontal-pursuit, 43% only for vergence-pursuit, and 41% for both. Thus, the majority of vermal pursuit P-cells modulated their activity during vergence-pursuit. These P-cells also discharged for vergence eye movements induced by step target-motion in-depth. The majority of vergence related P-cells carried convergence signals with both eye velocity and position sensitivities, and they discharged before the onset of convergence eye movements. Muscimol infusion into the sites where convergence P-cells were recorded resulted in a reduction of peak convergence eye velocity, of initial convergence eye acceleration, and of frontal-pursuit eye velocity. These results suggest specific involvement of the dorsal vermis in vergence eye movements.

Chapter 32 Further evidence for the specific involvement of the flocculus in the vertical vestibulo-ocular reflex (VOR)

We examined the simple-spike activity of floccular Purkinje (P) cells during sinusoidal pitch rotation and vertical optokinetic stimuli in alert, head-fixed cats. The great majority of pitch-responding P cells also responded to optokinetic stimuli with increased activity when the directions of the resultant eye movements were the same. During rapid modification of the VOR induced by visual pattern movement, modulation amplitudes of the cells tested increased together with the eye velocity increase. Maximal activation directions of these cells studied during vertical rotation in many planes were near the vertical canal planes. These results suggest that the activity of the majority of pitch-responding P cells contains a vertical eye velocity component during vestibular or optokinetic stimuli in addition to canal inputs during pitch rotation.

Role of the frontal eye fields in smooth-gaze tracking

Visual and vestibular senses are essential for appropriate motor behavior in three-dimensional (3D) space. Discovery of relevant specific subdivisions in sensory and motor pathways in recent decades has considerably advanced our understanding of the overall neural control of movement. Such subdivisions must eventually be further delineated into functional neural circuits for purposeful motor acts. Two critical questions are where in the brain do such circuits operate, and by what means. In this chapter, these issues are addressed for smooth tracking eye-movement systems in the simian. These results show that contrary to current understanding, synthesis of the functionally similar eye-movement systems, smooth-pursuit and vergence, takes place in the frontal cortex. This processing, which is of higher order than previously supposed, enables primates to track and manipulate objects moving in 3D space with the utmost of efficiency.

Similarity in Neuronal Firing Regimes across Mammalian Species

The architectonic subdivisions of the brain are believed to be functional modules, each processing parts of global functions. Previously, we showed that neurons in different regions operate in different firing regimes in monkeys. It is possible that firing regimes reflect differences in underlying information processing, and consequently the firing regimes in homologous regions across animal species might be similar. We analyzed neuronal spike trains recorded from behaving mice, rats, cats, and monkeys. The firing regularity differed systematically, with differences across regions in one species being greater than the differences in similar areas across species. Neuronal firing was consistently most regular in motor areas, nearly random in visual and prefrontal/medial prefrontal cortical areas, and bursting in the hippocampus in all animals examined. This suggests that firing regularity (or irregularity) plays a key role in neural computation in each functional subdivision, depending on the types of information being carried. SIGNIFICANCE STATEMENT By analyzing neuronal spike trains recorded from mice, rats, cats, and monkeys, we found that different brain regions have intrinsically different firing regimes that are more similar in homologous areas across species than across areas in one species. Because different regions in the brain are specialized for different functions, the present finding suggests that the different activity regimes of neurons are important for supporting different functions, so that appropriate neuronal codes can be used for different modalities.