In our earlier study of amygdaloid kindling in Papio papio (Pp), the development of partial complex seizure and of focal motor seizure was correlated with bifrontal theta discharge and increasing Rolandic spike discharge respectively and the final stage was characterized by primary generalized convulsive seizure. Since the latter seizure pattern is known to originate from the frontal focus in man, the frontal cortex became suspect in the development of the final stage seizure pattern. Daily prefrontal stimulation showed that Pp can be kindled from this site, culminating in a recurrent spontaneous seizure state identical to that induced by amygdaloid kindling in this species. However, our observation did not support our original assumption regarding the genesis of primary generalized convulsive seizure. Prefrontal and amygdaloid kindling are significantly different with respect to morphology, distribution and propagation of afterdischarge and interictal spike discharge, and speed and pattern of clinical seizure development. Most intriguingly, inter-ictal behavioral aberration associated with depth EEG changes was observed only in the prefrontal animals and not in the amygdaloid animals.

Postural or Parkinson-like tremor, which results from the impairment of mechanisms which are predominantly lateralized in the brain, is most likely related to the combined impairment of the dopaminergic nigrostriatal pathway and the corresponding rubro-olivo-cerebello-rubral loop (without excluding the possibility that other nervous mechanisms interconnected with these structures may represent an alternative disturbance). The integrity of the internal division of the pallidum and the ventrolateral area of the thalamus and their efferent fibers as well as the motor cortex and certain of its cortico-subcortico-spinal pathways (Figures 1 and 2) is apparently an essential feature for the elaboration of the rhythmic bursts associated with the appearance of postural tremor. The integrity of the spinal sensory roots and the rubro-tegmentospinal tract is not a prerequisite for the expression of postural tremor, a condition which seems essential for the production of rigidity. The latter facts suggest that the disturbances which subserve these two types of motor impairment, often concomitantly present in Parkinsonism, partially involve the impairment of different mechanisms although the loss of the DA fibers originating in the substantia nigra and ending in the neostriatum (Figure 1) appears to represent a disturbance common to both types of disorders.

Bradykinesia which may be associated with an impairment of catecholamine metabolism (and more especially the neostriatal DA mechanisms) on both sides of the brain may also result from bilateral lesions of the pallidum or of its outflow corresponding, in the main, to the pallidothalamic fibers ending in the ventrolateral thalamus. The latter types of lesion most likely exclude the influence of the monoaminergic, cholinergic and gabaminergic activities normally originating in the striopallidal system and influencing the activity transmitted to other CNS mechanisms. Severe akinesia, however, apparently depends on more profound and generalized disturbances of brain monoamine metabolism with or without the involvement of other ill-defined mechanisms. At any rate the impairment of the brain DA mechanisms (and especially those of the neostriatum) seems to represent a major feature in the production of the Parkinsonian type of akinesia. Further work is needed to establish the relative importance of the loss of catecholaminergic mechanisms other than those of the neostriatum in the production of akinesia.

Our observation of amygdaloid seizure development in cats indicated early afterdischarge propagation into basal cortical areas prior to the development of bifrontal sharp theta discharge. In view of the implied participation of the frontal lobe in amygdaloid kindling, both fractional lesioning and kindling of selective areas were performed. This paper summarizes our stimulation study involving premotor, prefrontal, mesial frontal and orbital cortices. Except for the orbital series which showed a rather strikingly similar pattern of seizure development to that of amygdaloid kindling, all areas showed significantly different features in terms of the speed of seizure development, afterdischarge propagation, fragility of developing seizure, final stage 5 seizure and post-ictal behavior pattern, interictal discharge morphology and propagation, and generalized seizure triggering threshold intensity. All these findings suggest that the frontal lobe participates in, but is not essential for, the amygdaloid seizure development. The results of ongoing fractional lesion series support such a conclusion.

To test the hypothesis that the cortex participates in amygdaloid kindling in rats, bilateral aspiration lesions were made in various cortical areas in rats prior to kindling. Lesions in orbital cortex (on the dorsal lip of the rhinal sulcus) or prefrontal cortex (area 10) significantly retarded the rate of amygdaloid kindling; lesions in motor cortex, anterior cingulate cortex, or visual cortex were without effect. Detailed analysis indicated that the orbital lesioned and frontal-lesioned rats kindled relatively normally up to the second-last stage of amygdaloid kindling, in which stage they perseverated significantly longer than the controls and the other lesioned rats. These results suggest that areas of the frontal lobe participate in the elaboration and generalization of amygdaloid seizures in rats. Although retarded in rate, kindling nonetheless occurred in the lesioned rats, indicating that these cortical areas are not essential for the development of amygdaloid seizures.

Theories of function of the cerebellum and basal ganglia are examined in the light of recent experimental findings obtained with the local cooling method, and both are matched against clinical observations. Evidence is summarized for a programming and initiating role in monkeys’ elbow movements of the lateral, and to a lesser degree, intermediate, cerebellum. Cooling either nuclei affected movements, but neither seemed to be important for precentral cortical unit discharge accompanying compensation for suddenly applied load pulses. The globus pallidus seemed to be importantly involved in movement guidance in the absence of vision.

A primary control system for the arm position is formulated. The hypothesis that the cerebellum is a part of the system controller is checked by studying the nerve cells responses in the cerebellum, and motor cortex, to natural activation of muscular receptors. The results show that the cerebellum receives feedback information related to the speed of these receptors. The discussion concentrates on how the interruption of this feedback may result in excessive oscillations to instability. These observations are the base for evaluating how the cerebral lesions produce dismeasurements.

Central feedback pathways for motor control were studied by recording EMG responses to sudden upper limb displacements in humans and monkeys using a precision torque motor to generate step load changes. Normal human subjects showed three short-latency EMG responses (Ml, M2 and M3) which appear to correspond to those recorded from trained monkeys. The M2 and M3 components, thought to represent feedback in supraspinal pathways, were significantly increased when the subjects were instructed to actively compensate for the load changes.

Parkinsonian patients with rigidity showed evidence of markedly increased feedback over the interval for the M2 and M3 responses and appeared to have lost the ability to modulate feedback according to the motor task being performed. The results are discussed with reference to recent research on motor control mechanisms in primates and a tentative model for the basis of Parkinsonian rigidity is proposed.

Experiments in humans and in monkeys have indicated that load perturbations, occurring during voluntary movements and postural activity, may be automatically compensated for. Overall muscle stiffness opposing load changes is determined by the viscoelastic properties of the muscle, by segmental reflex actions and finally by long-loop reflexes. Under certain circumstances, for instance when the subject or the experimental monkey is “prepared” to counteract perturbations which are unpredictable in time, the long-loop “reflexes” appear to be responsible for most of the corrective muscle tension. Experiments in anaesthetized monkeys revealed that signals from stretch afferents reach neurons of the motor cortex, possibly via a relay in the cortical area 3a. The latencies of these responses to well controlled muscle stretches were in the same range as motor cortical cell discharges recorded in alert monkeys subjected to load perturbations. Furthermore, these responses of cells in the motor cortex also had the appropriate timing to indicate a causal relationship with the long-latency electromyographic responses to load changes referred to above. These experimental results therefore strongly support the hypothesis, first proposed by Phillips (1969), of a transcortical servoloop adjusting motor cortical output according to the load conditions in which movements are performed.

The major advantage of transcortical regulations as opposed to segmental regulations, seems to be a powerful gain control acting at the cortical level; it was repeatedly shown that the long-loop reflexes are strongly modifiable and under voluntary control. It is suggested that an adaptive gain control at the cortical level is a prerequisite to preserve the complex capabilities of the motor cortex as the chief "executive" for skilled, preprogrammed movements. A loss of this adaptive gain control may be, at least partly, the cause of motor disorders such as rigidity in Parkinsonian patients, as reported by Tatton and Lee (1975). It is suggested that further investigations of the control of transcortical reflexes may aid in the understanding of the pathophysiology of motor disabilities.

Decorticate spasticity in the squirrel monkey was chosen as a convenient laboratory model of spasticity capable of quantitative assessment upon which to evaluate various currently popular clinical spasmolytic measures. The effects of a wide variety of cortical lesions were studied involving primary and supplementary motor, premotor and parietal cortex unilaterally and bilaterally, measuring muscle tone with the evoked integrated E.M.G. technique. Measurable spasticity resulted only if primary motor cortex was ablated bilaterally usually but not always preferentially involving biceps brachii and quadriceps. Resulting postures were variable offering no justification for the term “decorticate posture”. The integrated evoked E.M.G. was proportional to rate of stretch and chiefly phasic in type as in hemiplegic man. Stereotactic dentatectomy resulted in profound ipsilateral reduction in this spasticity, but was without effect in intercollicular or anemic decerebrate cats. The mechanism of the spasticity and of the cerebellar effects are discussed.

It was with considerable hesitation that I finally accepted the kind invitation of Vernon Brooks and the Organizing Committee of this Symposium to say a few words at the end giving some of my impressions of the presentations and discussion and reflections on the remarkable advances in our knowledge of motor systems that has occurred during recent years. I have been asked also if I would try to place some of these findings from experimental laboratories in the context of clinical experience with diseases and disorders of motor control. I would like to draw particular attention to the importance of state dependent reactions in which patterns of behavior are set up, even including spinal reflexes, by present programs depending on the general or directional reactive state of the organism.