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Biomedical subjects

F P Kolb

Publications and source records attributed to F P Kolb.

17 recordsLinked to original sources

Inactivation of interposed nuclei in the cat: classically conditioned withdrawal reflexes, voluntary limb movements and the action primitive hypothesis.

The cerebellar interposed nuclei are considered critical components of circuits controlling the classical conditioning of eyeblink responses in several mammalian species. The main purpose of the present experiments was to examine whether the interposed nuclei are also involved in the control of classically conditioned withdrawal responses in other skeletomuscular effector systems. To achieve this objective, a unique learning paradigm was developed to examine classically conditioned withdrawal responses in three effector systems (the eyelid, forelimb and hindlimb) in individual cats. Trained animals were injected with muscimol in the cerebellar interposed nuclei, and the effects on the three conditioned responses (CRs) were examined. Although the effects of muscimol were less dramatic than previously reported in the rabbit eyeblink preparation, the inactivation of the cerebellar nuclei affected the performance of CRs in all three effector systems. In additional experiments, animals were injected with muscimol at the sites affecting classically conditioned withdrawal responses to determine the effects of these injections on reaching and locomotion behaviors. These tests demonstrated that the same regions of the cerebellar interposed nuclei which control withdrawal reflexes are also involved in the control of limb flexion and precision placement of the paw during both locomotion and reaching tasks. The obtained data indicate that the interposed nuclei are involved in the control of ipsilateral action primitives and that inactivating the interposed nuclei affects several modes of action of these functional units.

Animals

Non-motor associative learning in patients with isolated degenerative cerebellar disease.

In recent decades it has become clear that the cerebellum is involved in associative motor learning, but its exact role in motor learning as such is still controversial. Recently, a contribution of the cerebellum to different cognitive abilities has also been considered, but it remains unclear whether the cerebellum contributes to cognitive associative learning. We compared nine patients with an isolated cerebellar degenerative disease in a cognitive associative learning task with 10 controls. Patients and controls were matched for age, sex, handedness, level of education, intelligence and capabilities of visual memory. The subjects were asked to learn the association between six pairs of colours and numerals by trial and error. Additionally, a simple reaction time and a visual scanning test were conducted in order to control for the influence of motor performance deficits in cerebellar patients. In comparison with the controls, it took the patients significantly longer to learn the correct associations between colours and numerals, and they were impaired in recognizing them later on. Two patients showed no associative learning effect at all. Neither the simple reaction time nor the visual scanning time correlated substantially with the results of associative learning. Therefore, motor-associated disabilities are unlikely to be the reason for the learning deficit in cerebellar patients. Our results suggest that the cerebellum might contribute to motor-independent processes that are generally involved in associative learning.

Aged

Involvement of the human cerebellum during habituation of the acoustic startle response: a PET study.

The present study investigated the involvement of the human cerebellum in the habituation of the acoustic startle response using PET. The startle response was elicited in seven young, healthy subjects by a tone presented via headphones. Startle responses were recorded from the right sternocleidomastoid muscle. Regional cerebral blood flow (rCBF) was assessed in nine scans and one startle stimulus was applied during each scan. The reduction of size of the sternocleidomastoid muscle response was correlated with changes in rCBF during the ongoing process of startle response habituation. A significant decrease of rCBF was found in the medial cerebellum. These data are consistent with an involvement of the medial parts of the human cerebellum in non-associative learning as proposed by previous animal studies.

Acoustic Stimulation

Conditioned and unconditioned forelimb reflex systems in the cat: involvement of the intermediate cerebellum.

Temporary inactivation of the cerebellar interposed nuclei was used to assess the role of the intermediate cerebellum in the performance of forelimb cutaneo-muscular reflexes in the cat. The following types of reflexive responses were evaluated: the classically conditioned and unconditioned forelimb withdrawal responses and the forelimb tactile placing, hopping and magnet responses. The experiments tested the hypothesis that the intermediate cerebellum is involved in the performance of all the above forelimb reflexes. The forelimb withdrawal reflex was classically conditioned in a newly developed paradigm in which animals were first operantly conditioned to stand on four elevated platforms. Trained animals were microinjected with a gamma-aminobutyric acid (GABA) agonist, muscimol, in the interposed nuclei, and the effects of inactivation of the intermediate cerebellar output on the forelimb reflexes were examined. The main findings of these experiments are that unilateral muscimol inactivation of the interposed nuclei in the cat abolished the expression of the classically conditioned limb flexion reflex, suppressed the performance of the unconditioned withdrawal reflex and, in parallel, down-regulated the tactile placing, hopping and magnet postural responses in the ipsilateral forelimb. These observations are inconsistent with concepts indicating exclusive involvement of the intermediate cerebellum in the classically conditioned reflexes elicited by aversive stimuli. On the contrary, they support the hypothesis of a more global involvement of this structure in learned and unlearned defensive flexion reflexes and in automatic postural response systems.

Animals

A reliable method for sustaining a pre-defined pre-innervation level.

Numerous experimental approaches are based on evaluating electromyographically recorded muscle activity. Some experiments require a certain level of pre-innervation in a muscle or muscle group whereas others must avoid this. Measured parameters, such as the time to onset of the muscle response to an electrical stimulus, etc., depend critically on the level of pre-innervation. The pre-innervation level is most commonly estimated from parameters such as the force generated by this muscle or the upright posture of a human subject. These methods, however, are indirect and may yield erroneous results. This paper describes an inexpensive method developed for a wide range of applications in muscle-tonus-based experiments, in which the tonus is precisely controlled. A simple electronic circuit is presented by which the level of muscle pre-innervation is directly recorded, monitored and - depending on the experimental approach - also fed back to the subject. Physiological experiments on the flexion reflex in healthy human subjects document the reliability of our electronic device.

Electromyography

Spatial distribution of field potential profiles in the cat cerebellar cortex evoked by peripheral and central inputs.

The present study was designed to characterize the spread of excitation within the frontal plane of the cat cerebellar cortex following different types of stimuli. In particular, experiments were performed to determine whether the spread of excitation evoked by mossy fibre inputs proceeds primarily along the parallel fibres ("beam-like" spread) or whether these inputs activate non-propagated foci ("patches") in the cerebellar cortex. Field potentials were recorded within a frontal plane as a medial to lateral array at different depths in parallel tracks. The recordings were made following electrical stimulation of different forelimb nerves and functionally related areas of the sensorimotor cortex as well as during passive paw movements. The resulting spatial grid of responses provides discrete spatio-temporal information reflecting the activation of specific cerebellar afferents and the neuronal interactions they evoke. The method employed demonstrates the spatial distribution of the temporal sequence of excitability changes throughout all the cerebellar cortical layers. In general, the characteristics of the responses in the intermediate cerebellar cortex depended on the source of the signals. Activity patterns evoked by peripheral nerve stimulation showed more clustered foci compared with those following electrical stimulation of functionally related areas of the sensorimotor cortex. The centrally evoked profiles were generally more homogeneous. The largest number of foci were observed following passive movements around the wrist joint. The spread of excitation in the vertical direction was evaluated by the spatial shift of the line of reversal of the N3/P2-potential (zero-isopotential line). Lines of reversal for peripherally-evoked activity patterns were approximately 90 microns closer to the molecular layer than those evoked by central stimulation in animals in which recordings have been performed in lobule Vc. The opposite was found for recordings in lobule Vb, where potential reversals following peripheral stimulation were located 40 microns deeper than those evoked following central stimulation. Cortical inputs resulted in a more proximal activation of lobule Vc Purkinje cell dendrites than in lobule Vb. This type of input processing thus seems to be lobule dependent. A beam-like spread of excitation could not be demonstrated. For both climbing fibre and mossy fibre afferent systems multiple foci were found in the frontal plane. The foci due to mossy fibre activation arose from the granular layer and expanded vertically to the molecular layer. For the climbing fibre system the foci were restricted to the molecular layer, where they merged to form a superficial band of activation. Although the data presented in this paper favour a focal distribution of activity, they do not exclude beam-like propagation along the parallel fibres, because of the difficulty of detecting this pattern in response to the stimuli. The "beam"- and "patch"-like hypotheses need not be mutually exclusive. Each could contribute to a specific stage of the temporal-spatial processing in the cerebellar cortex in a functional and task-specific manner.

Animals

Cerebellar activation during classical conditioning of the human flexion reflex: a PET study.

The present study investigated the involvement of the cerebellum in classical conditioning of the cutaneomuscular flexion reflex in four normal volunteers using positron emission tomography (PET). The flexion reflex was elicited by electrical pulses applied to the medial plantar nerve (unconditioned stimulus, US). A tone was presented as the conditioning stimulus, which co-terminated with the US. The incidence of conditioned responses was correlated with changes in rCBI during the acquisition process of flexion reflex conditioning. Blood flow was significantly increased in an area extending from the ipsilateral cerebellum and hippocampus to bilateral frontal regions (p = 0.009). These data provide support for an involvement of the cerebellum as well as hippocampus among other neural systems in classical flexion reflex conditioning.

Adult

Classical conditioning of the human flexion reflex.

The eyeblink conditioning paradigm is a well established model for studying learning processes in humans and animals. In this study a flexion reflex conditioning paradigm was established using the standard delay paradigm. The flexion reflex was elicited in 10 young, healthy subjects by a train of electrical pulses (100 ms, 100 Hz, 0.65 ms) applied to the medial plantar nerve (unconditioned stimulus, US). A tone (1000 Hz, 550 ms) was presented via headphones as the conditioning stimulus and which coterminated with the US. Responses were recorded from the anterior tibial muscles. Subjects were conditioned within one session of 120 trials of paired stimuli. This was established statistically via the continuous change in characteristic parameters of the responses throughout the experiment. Although the process of limb muscle conditioning takes longer than eyeblink conditioning, this type of flexion-reflex conditioning may possibly serve as a further model for the study of plastic changes within the nervous system. Moreover, the considerable versatility of limb movements offers the advantage of greater possibilities for testing the conditioning result.

Adult

Characteristics of posture alterations associated with a stepping movement in cats.

The relationship between changes in posture and the performance of a forelimb movement required for a transition between two stance positions was analysed in cats. The task consisted of an operantly conditioned, forelimb stepping movement from one support platform to another located more anterior. The reward was given only after a specific vertical force was applied to the second platform. This ensured that the cat performed a clear transition from its initial stance posture to another requiring a different weight distribution. The strategy adopted by an animal during the conditioned movement was studied by analysing the distribution of the vertical forces as a function of time. Specific quantitative functions were used to describe the weight distribution in the anterior-posterior, right-left and diagonal directions as the task was performed. The temporal parameters characterising this behaviour were not significantly different between animals, except for reaction times. In contrast, spatial parameters reflected in the distribution of vertical forces generated during the performance of the task were characteristic for each animal. As a consequence, a variety of strategies were employed. Nevertheless some general features were found, including the persistence of a diagonal support pattern during the phasic part of the movement, and an initial movement to the side of the forepaw performing the movement. The findings support the view that each animal exhibits a specific strategy for performing this well-learned task, and that the strategy is consistently employed over consecutive trials of the movement.

Animals

Comparative analysis of cerebellar unit discharge patterns in the decerebrate cat during passive movements.

1) The present experiments were undertaken to study how information about the parameters of a passive movement is processed at different neuronal levels of the cat cerebellar cortex. The analysis has been performed by recording extracellularly in the intermediate part of the cerebellar anterior lobe from presumed mossy fibres, presumed granule cells, and Purkinje cells with simple spikes and complex spikes. 2) The discharge patterns obtained during passive movements of the cat's forepaw were characterized by components which could be related to dynamic or static parameters of the movement. With respect to the occurrence of dynamic responses, patterns were classified according to a statistically derived measure in three different types. By using the same statistical measure, discharge patterns were additionally classified into two subgroups according to their response components reflecting static parameters. Within the patterns a clearcut relationship between dynamic and static components was observed. The corresponding distributions are shown and discussed. 3) A very interesting result of the classification of cerebellar discharge patterns is that the distribution of the different types depended on the level of integration within the cerebellar cortex. Patterns of the low scale integrated cerebellar input (mossy fibre-system), as well as those of granule cells (the first cerebellar computational niveau), reflected both static and dynamic movement parameters. At the Purkinje cell level (a level with a high degree of convergence) the discharge patterns are characterized predominantly by dynamic responses. 4) The interrelationship between complex- and simple spikes of Purkinje cells was tested by different methods: a) By analyzing the paired values of the mean complex-(CS) and simple spike (SS) discharge probabilities of 110 Purkinje cells a scatter was obtained, indicating an underlying hyperbolic relation (prob(CS) = a/(prob(SS]b). Thus, a high CS discharge probability is accompanied by a low SS probability and vice versa. b) The timelocked complex- and simple spike responses were studied by comparing the similarity of their responses. All combinations of complex- and simple spike patterns were observed, ranging from a sign correct similarity to a mirror image similarity. The distribution of the measure for similarity shows that the mirror image predominated. c) The individual simple spike discharge probability is characterized by a pause evoked by the occurrence of a complex spike event. The simple spike discharge probabilities during an interval preceding and following a complex spike event were compared.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals

Cerebellar unit responses of the mossy fibre system to passive movements in the decerebrate cat. I. Responses to static parameters.

1) Experiments were designed to detect how static parameters of natural, passive hand movements are encoded and integrated within the cerebellar cortex. For this purpose unit activity was recorded extracellularly from presumed mossy fibres (MF), presumed granule cells (GrC) and from Purkinje cells (PC) discharging with simple spikes (SS) and complex spikes (CS). With respect to the PC, our interest was focussed primarily on the SS activity. The recordings were performed in the intermediate part of the cerebellar anterior lobe of decerebrate cats. The animal's forepaw was passively moved around the wrist joint by an electronically controlled device. The movements were exactly reproducible so that peristimulus time histograms of the unit activity could be constructed. 2) At the input level (MF) and at the first level of integration within the cerebellar cortex (GrC), patterns with similar discharge characteristics were found. Such patterns could, to a limited extent, also be detected at the cerebellar output (SS of PC). However, in most cases of SS discharge, patterns were found with weak correlation between the tonic activity and static parameters of the movements. 3) Absolute paw position, amplitude, and duration of movements were found to be related over wide ranges to the activities of MF and GrC. Absolute position is directly encoded by tonic discharge during the low or high holding phases. Beside this, units were found without a correlation between the tonic discharge and the position of the nonmoving paw. However, in these units it was sometimes observed that the information about the momentary position or the information about the mean position was sometimes conveyed exclusively during the proceeding upward or downward movement. Thus, information about static parameters was transmitted only at times when a dynamic parameter (such as velocity) occurred. This type of position information encoding is termed "indirect mode of transmission". 4) A specific relationship between SS unit activity of PC and the absolute position of the forepaw or amplitude of the movement could be found primarily by using multiple ramps instead of single ramp movements. This was observed even if both types of ramp movements had the same velocity, individual amplitude, and tested range. However, on multiple ramp movements the paw generally remained for a shorter period at a specific position level as compared to the single ramp movements. 5) Apart from this timing phenomenon, a late movement response was observed, which results in a specific type of position information encoding on multiple ramp functions.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals

Cerebellar feedback signals of a passive hand movement in the awake monkey.

From three intact and awake monkeys, 149 Purkinje cells and 44 presumed mossy fibres were recorded in the intermediate part of the cerebellar anterior lobe, and this activity was analyzed with regard to different parameters of a passive hand movement. The tonic discharge rate of the simple spikes (SS) varied according to different joint positions only in a single Purkinje cell, whereas such a position relation was found in nine out of 44 presumed mossy fibres. A phasic increase of the complex spike (CS) discharge rate of Purkinje cells in response to passive wrist movements usually occurred within 100 ms after movement onset. However, in some units a phase of increased CS rate was observed which lasted for the whole movement duration. The amount of this phasic increase in the CS rate depended on the acceleration of movement, but the SS response to movements of different velocity remained unchanged.

Afferent Pathways

A simple method for reliable separation of cerebellar Purkinje cell complex and simple spikes.

During the analysis of cerebellar Purkinje cell firing the use of two level discriminators for the separation of complex spike (CS) and simple spike (SS) can produce "wrong SS-events", since the amplitude of the CS wavelets may exceed the discrimination level for the SS. This is also the case, when the initial spike of the CS is negatively deflected. A logic circuit was developed, which ensures reliable separation of the two types of spike by a mutual control of the two channels. The CS wavelet events are obtained via an additional channel.

Animals

Simple and complex spike activity of cerebellar Purkinje cells during active and passive movements in the awake monkey.

Two Rhesus monkeys (Macaca mulatta) were trained to pursue a target light signal by moving the hand at the wrist joint. Additionally, a d.c. motor could be attached to the lever in order to perform similar passive movements. During performance of the task, single Purkinje cells were recorded from the intermediate part of the cerebellar anterior lobe. Electromyographic activity of the flexor and extensor muscles of the forearm was recorded simultaneously. Passive hand movements evoked changes in the complex spike and simple spike discharge of Purkinje cell. The complex spike responded most sensitively to the beginning of the movement; the activity pattern had phasic character and could be related specifically to the movement direction. The simple spike response was usually weak and hence revealed-less specific relations. During active movements the simple spike frequency change was generally stronger than during passive movements and reached a maximum (or minimum) at the beginning of hand deflexion. The complex spike activity during active movements was characterized by a contrast between the time phases before and after the movement onset. In most of the cases, where a phase of increased activity stopped at the movement onset, the sensory feed-back signal seen during passive movements was cancelled. The possible consequences of the convergence of the complex and simple spike signal for the motor control function of the cerebellum are discussed.

Action Potentials

Information about peripheral events conveyed to the cerebellum via the climbing fiber system in the decerebrate cat.

Discharges of Purkinje cells (PCs) with simple (SS) and complex spikes (CS) in the c1-zone of lobule Vc of the anterior lobe of the cerebellar cortex were analyzed in the decerebrate cat during a passive movement of the cat forepaw. The CS of the PC responded differentially and/or proportionally to the position of the extremity, amplitude of the movement, velocity and acceleration. Inphase and outphase responses of the climbing fiber (CF) system to sinusoidal movements could depend on the position of the extremity within the operational range. From these results we deduce that peripheral events can be signalled by the CF system. The possible function of the interaction between the two inputs at the PC level is discussed.

Animals

Responses of cerebellar units to a passive movement in the decerebrate cat.

The responses of mossy fibers (MF), granular cells (GrC) and Purkinje cells (PC) were recorded in the cerebellum of the decerebrate cat during a passive movement about the forepaw wrist joint. Three main discharge patterns containing information about all the static and dynamic parameters of the movement were found. Simultaneous recording of complex spikes (CS) and simple spikes (SS) showed that the activity of PC can be modulated through either MF or CF input channels alone or both together. In the latter case SS and CS discharge most commonly showed an opposite behavior, in which the increase of the frequency of one type of spike was accompanied by a decrease of the frequency of the other type. Both inputs displayed tonic and phasic characteristics and all the qualitative discharge patterns observed. Therefore it was concluded that aside from differences in the discharge frequency, both inputs are able to directly signal peripheral events.

Animals