Psychological Studies of Chronic Cerebellar Stimulation in Man

1. A detailed theory of cerebellar cortex is proposed whose consequence is that the cerebellum learns to perform motor skills. Two forms of input-output relation are described, both consistent with the cortical theory. One is suitable for learning movements (actions), and the other for learning to maintain posture and balance (maintenance reflexes).2. It is known that the cells of the inferior olive and the cerebellar Purkinje cells have a special one-to-one relationship induced by the climbing fibre input. For learning actions, it is assumed that:(a) each olivary cell responds to a cerebral instruction for an elemental movement. Any action has a defining representation in terms of elemental movements, and this representation has a neural expression as a sequence of firing patterns in the inferior olive; and(b) in the correct state of the nervous system, a Purkinje cell can initiate the elemental movement to which its corresponding olivary cell responds.3. Whenever an olivary cell fires, it sends an impulse (via the climbing fibre input) to its corresponding Purkinje cell. This Purkinje cell is also exposed (via the mossy fibre input) to information about the context in which its olivary cell fired; and it is shown how, during rehearsal of an action, each Purkinje cell can learn to recognize such contexts. Later, when the action has been learnt, occurrence of the context alone is enough to fire the Purkinje cell, which then causes the next elemental movement. The action thus progresses as it did during rehearsal.4. It is shown that an interpretation of cerebellar cortex as a structure which allows each Purkinje cell to learn a number of contexts is consistent both with the distributions of the various types of cell, and with their known excitatory or inhibitory natures. It is demonstrated that the mossy fibre-granule cell arrangement provides the required pattern discrimination capability.5. The following predictions are made.(a) The synapses from parallel fibres to Purkinje cells are facilitated by the conjunction of presynaptic and climbing fibre (or post-synaptic) activity.(b) No other cerebellar synapses are modifiable.(c) Golgi cells are driven by the greater of the inputs from their upper and lower dendritic fields.6. For learning maintenance reflexes, 2(a) and 2(b) are replaced by2'. Each olivary cell is stimulated by one or more receptors, all of whose activities are usually reduced by the results of stimulating the corresponding Purkinje cell.7. It is shown that if (2') is satisfied, the circuit receptor --> olivary cell --> Purkinje cell --> effector may be regarded as a stabilizing reflex circuit which is activated by learned mossy fibre inputs. This type of reflex has been called a learned conditional reflex, and it is shown how such reflexes can solve problems of maintaining posture and balance.8. 5(a), and either (2) or (2') are essential to the theory: 5(b) and 5(c) are not absolutely essential, and parts of the theory could survive the disproof of either.

1. Stimulation of the reticular formation of the brain stem evokes changes in the EEG, consisting of abolition of synchronized discharge and introduction of low voltage fast activity in its place, which are not mediated by any of the known ascending or descending paths that traverse the brain stem. The alteration is a generalized one but is most pronounced in the ipsilateral hemisphere and, sometimes, in its anterior part. 2. This response can elicited by stimulating the medical bulbar reticular formation, pontile and midbrain tegmentum, and dorsal hypothalamus and subthalamus. The bulbar effect is due to ascending impulses relayed through these more cephalic structures. The excitable substrate possesses a low threshold and responds best to high frequencies of stimulation. 3. Some background synchrony of electrocortical activity is requisite for manifestation of the response. In the "encephale isolé", reticular stimulation has no additional effect upon the fully activated EEG. With synchrony, in spontaneous drowsiness or light chloralosane anesthesia, the effect of reticular stimulation is strikingly like Berger's alpha wave blockade, or any arousal reaction. In full chloralosane anesthesia, high voltage slow waves are blocked but no increase in lower amplitude, fast activity occurs. With barbiturate anesthesia, the reticular response is difficult to elicit or is abolished. 4. In the chloralosane preparation, the secondary cortical response evoked by a sensory volley is generally unaffected by reticular stimulation. Consequent sensory after-discharge is abolished, however, as is pyramidal tract discharge and jerky movements referable to it. Outside the sensory receiving area, secondary responses themselves may be reduced or prevented. 5. The convulsive spikes produced by local strychnine and those of a fit following supramaximal cortical excitation, are not decreased by stimulating the reticular formation. 6. The cortical recruiting response induced by low frequency stimulation of the diffuse thalamic projection system is reduced or abolished by reticular stimulation. 7. There is some indication that the cortical effect of reticular stimulation may be mediated by this diffuse thalamic projection system, for synchronized activity within it is similarly prevented by reticular excitation, and direct high frequency stimulation of this system, within the thalamus, reproduces the reticular response. It is possible, however, that other mechanisms may be involved in its mediation. 8. The reticular response and the arousal reaction to natural stimuli have been compared in the "encéphale isolé", in which EEG synchrony was present during spontaneous relaxation or was produced by recruiting mechanisms, and the two appear identical. 9. The possibility that the cortical arousal reaction to natural stimuli is mediated by collaterals of afferent pathways to the brain stem reticular formation, and thence through the ascending reticular activating system, rather than by intra-cortical spread following the arrival of afferent impulses at the sensory receiving areas of the cortex, is under investigation. 10. The possibility is considered that a background of maintained activity within this ascending brain stem activating system may account for wakefulness, while reduction of its activity either naturally, by barbiturates, or by experimental injury and disease, may respectively precipitate normal sleep, contribute to anesthesia or produce pathological somnolence.