Ranulfo Romo

Production and suppression of tremor by mesencephalic tegmental lesions in monkeys.

Abstract In a group of rhesus monkeys two consecutive lesions were placed in the mesencephalic tegmental region. The first lesion, for tremor production, was placed ventromedially in a region where multiunit activity was organized in rhythmic bursts of 4 to 8 cps and threshold electrical stimulation induced III nerve type of responses. The second lesion, for tremor suppression, was placed dorsolateral to the previous one, in a region where nonrhythmic multiunit activity was enhanced by peripheral nociceptive stimulus and threshold electrical stimulation produced awakening. Studying the lesions by planimetry in a quantitative manner, it was found that tremor production depended on the involvement of a critical amount of the pars compacta of the substantia nigra and the region immediately behind it, whereas tremor suppression depended on the involvement of a critical amount of the nucleus reticularis mesencephali. Involvement of other adjacent structures was not significant for either tremor production or suppression.

Subcortical Correlates of the Auditory Brain Stem Potentials in the Monkey: Bipolar EEG and Multiple Unit Activity Responses

Bipolar EEG and multiple unit activity (MUA) responses correlated to the vertex auditory brain stem potentials (ABSP) were recorded in different brain stem and diencephalic primary auditory pathways and other anatomically related structures of large monkeys under barbiturate anesthesia. Bipolar EEG responses were recorded bilaterally to monaural stimulation and were formed by 3 or more of 6 consecutive components labeled A, B, C, D, E and F (peak latencies of 3.8, 4.2, 4.6, 5.0, 7.8 and 11.8 msec) correlated in latency with waves III, IV, V, VI, VII and SP3 of the ABSP, respectively. Component B was prominent and showed clearcut reverse polarity at the trapezoid body (TB) and superior olivary complex (SOC), while components C and F inverted and everted polarity at the mesencephalic reticular formation (MRF) and medial geniculate nucleus thalami (MG). Subcortical MUA peaks A, B, C, D and E time locked to the stimulus presentation correlated in latency to those of the bipolar EEG responses. In addition, a significant correlation was found between percentage amplitude of the subcortical EEG response components and MUA peaks in different structures contra- (r = 0.847) and ipsilateral (r = 0.973) to the stimulated ear. Although a single wave of the vertex ABSP correlated in latency with more than one response component in different subcortical loci, amplitude of component A was significantly larger (P less than or equal to 0.02) at TB ipsilateral, B at TB and SOC bilateral, and C and F at MRF, and D and E at MG contralateral to the stimulated ear.

Specific and nonspecific multiple-unit activities during pentylenetetrazol seizures in animals with pretrigeminal brain stem transection

Abstract The sequence of activation and deactivation of multiple-unit activity (MUA) in the mesencephalic and pontine reticular formations, pyramidal tract, and the electromyogram (from neck and temporalis muscles) in relation to the onset and the end of EEG paroxysmal discharges induced by pentylenetetrazol was studied in cats with brain stem “pretrigeminal” transection. The following events were observed: (i) A significant increment of the MUA in the mesencephalic reticular formation followed 6 s later by the onset of EEG paroxysmal discharges and significant increase of pyramidal tract MUA, while pontine reticular MUA increased slowly before or after the onset of EEG paroxysmal discharges and the electromyogram remained unchanged. (ii) A decrease of mesencephalic reticular and pyramidal tract MUA at the end of EEG paroxysmal discharges, while the pontine reticular MUA remained very active. Comparing the observations made in “pretrigeminal” preparations with those previously published in “encephale isole” preparations, we conclude that in normal conditions pentylenetetrazol induced a peculiar sequence of activation of MUA starting at the mesencephalic reticular formation and followed by other brain stem structures and the cerebral cortex, that the mesencephalic reticular seizures propagate to the spinal cord through both pyramidal and “extrapyramidal” (perhaps the brain stem motor apparatus) pathways, and that inhibitory mechanisms of seizure activity in this model of epilepsy, situated above the transection level, exclude the cerebellum.

Carbachol “push-pull” perfusion in the reticular formation: Effect on the contiguous multiple-unit activity and other sleep-waking parameters in cats

Abstract The effects of carbachol perfusion in the pontine (PRF) and mesencephalic (MRF) reticular formation on contiguous multiple-unit activity (MUA) and other sleep-waking parameters of cats were determined. Perfusion of carbachol into the PRF significantly increased the number of contiguous MUA neuronal spikes. There was a linear relationship between the number of minutes of perfusion and MUA neuronal spikes from the 1st to the 8th minute (estimated 1 to 8 μg), followed by a plateau of maximal MUA activation from the 8th to the 10th minute (estimated 8 to 10 μg), and a subsequent decrease in number of MUA cellular spikes from the 10th to the 11th minute (estimated 10 to 11μg) when the perfusion was discontinued. Concomitantly, the perfusion significantly decreased electromyographic MUA (hypotonia) but it did not systematically modify the mesencephalic reticular formation and other electrophysiologic and behavioral sleep-waking parameters. Perfusion of carbachol into the MRF significantly increased the number of contiguous MUA neuronal spikes. There was a linear relationship between the number of minutes of perfusion and the number of MUA neuronal spikes from the 1st to the 11th minute (estimated 1 to 11 μg) when the perfusion was discontinued. Concomitantly, the perfusion significantly increased electromyographic MUA (hypertonia) and produced a systematic electrophysiologic and behavioral arousal response.

Effect of Carbachol "Push-Pull" Perfusion in the Reticular Formation on Alumina Cream-Induced Focal Motor Seizures in Cats

Abstract The effect of carbachol perfusion in pontine (PRF) and mesencephalic reticular formations (MRF) on type B and C focal motor seizures induced by alumina cream was studied in a group of cats, in an attempt to reproduce (totally or partially) that observed under spontaneous sleep-waking states and state transitions. During carbachol perfusion in the PRF, there was a pure hypotonic response: significant decrease in mean tonic and phasic electromyographic multiple-unit activities (MUAs) with no changes in number of electroencephalogram (EEG) type B spikes and duration of type C paroxysmal discharges. This response lasted 60 to 80 min and was followed by a slow-wave-sleep-like response: further significant decrease in mean tonic and phasic electromyographic MUA and increase in number of EEG type B spikes and duration of type C paroxysmal discharges, which lasted until 180 min after carbachol perfusion. During carbachol perfusion in the MRF, there was an arousal-like response: significant increase in type B mean tonic and phasic electromyographic MUA and decrease in number of EEG spikes and prevention of occurrence of electroencephalogram-electromyogram patterns of type C seizures. This response lasted 60 to 80 min after perfusion and was followed by a paradoxical-sleep-like response: significant decrease in type B mean tonic and phasic electromyographic MUA and number of EEG spikes and delay of type C phasic electromyographic MUA and decreased duration of EEG paroxysmal discharges.

Effect of sagittal transections of the brain stem tegmentum on alumina cream-induced focal motor seizures in cats.

The effect of extensive and circumscribed sagittal transections of the brain stem tegmentum on types B (epilepsia partialis continua) and C (contradversive tonic-clonic seizures) alumina cream-induced focal motor seizures in cats was investigated. The neurological abnormalities of cats with transections and differences in the EEG-EMG patterns of types B and C seizures between operated and intact animals were statistically analyzed. Animals with either extensive or superior central nucleus transections showed bilateral neglect and internuclear palsy syndromes, no tonic type C seizures (contradversion), and a significant decrease in electromyogram multiple-unit activity (EMG MUA) from 0 to 10 s or more after the onset of EEG paroxysmal tonic-clonic discharges. Animals with rostral transections showed a unilateral neglect and internuclear palsy or ataxic syndromes with a concomitant partial reduction of contradversive seizures and a significant decrease in EMG MUA from 0 to 5 s or less after the onset of EEG tonic-clonic discharges; those with dorsal and caudal transections showed a transient neglect and insomniac syndromes with no differences in contradversion and EMG MUA at the onset of EEG tonic-clonic discharges in relation to intacts. Experimental and intact animals showed neither differences in types C and B EEG patterns nor in EMG MUA at the end of type C EEG tonic-clonic discharges and type B EEG spikes. These results support the idea that tonic and clonic muscular seizures are due to epileptic impulses originating in the cerebral cortex and mediated at the level of the brain stem by different pathways.

Specific and Nonspecific Multiple Unit Activities during the Onset of Pentylenététrazol Seizures. III. Animals with Ablations of the Cerebral Cortex

Summary: The effects of cortical ablations on behavior, wakefulness‐sleep states, and PTZ‐induced seizures were studied in a group of cats. Animals were divided in two groups: group I, animals with ablations of primary sensory cortices, including the primary somatosensory, visual, and auditory cortices; group II, animals with ablations of association cortices, including the parietal, cingulate, and orbitofrontal cortices. Animals of group I showed apathy, decreased visual and auditory reactivity, and postural defects. They showed no significant changes in wakefulness‐sleep states. Threshold doses of PTZ failed to induce EEG tonic‐clonic discharges but did increase multiple unit activity (MUA) of the motor cortex and the mesencephalic and pontine reticular formations, as has been reported for intact animals. In contrast, animals of group II showed variable degrees of hyperactivity, significant increase in the amount of wakefulness, and decrease in slow‐wave sleep, with no changes in paradoxical sleep. Threshold doses of PTZ induced EEG tonic‐clonic seizures that lasted 10 to 100 times as long as those seen in intact animals, and MUA increments of the motor cortex and mesencephalic and pontine reticular formations were significantly larger than those observed in group I and intact animals. These findings support the idea that association cortices modulate the wakefulness‐sleep states and exert an important inhibitory effect on the development of PTZ‐induced seizure activity at cortical and subcortical levels.

Effect of a new thienodiazepine (We-941) on sleep patterns of normal and insomniac subjects.

Abstract The effect of a new thienodiazepine We-941 (0.5 mg, oral) on sleep patterns of normal and insomniac subjects was quantitatively determined and statistically compared with (a) the sleep patterns obtained under base line conditions and with placebo in 10 normal subjects; (b) with those obtained under initial and final placebo in a series of 8 insomniac subjects; and (c) with those obtained with flurazepam (30 mg, oral) in another series of 8 insomniac subjects. 1. 1. The spontaneous arousal episodes shown by some normal subjects under base line conditions and with placebo were abolished by We-941. However, no significant differences in wakefulness-sleep parameters were found in normal subjects under We-941 compared with base line or placebo. 2. 2. The duration of wakefulness and number of arousal episodes were decreased by We-941 which increased the duration of sleep, decreased the latency of slow wave sleep I and II and increased the duration of slow wave sleep III. These results were significantly different to initial, but not to final, placebos in the same insomniac subjects. Flurazepam decreased the duration of wakefulness and number of arousal episodes and increased the duration of sleep and duration of rapid eye movement sleep. These results were significantly different from initial, but not from final, placebos in the same insomniac subjects. 3. 3. No significant differences were found between the effects of We-941 and flurazepam on slow wave sleep III and rapid eye movement sleep in different insomniac subjects.

Effect of carbachol and atropine perfusions in the mesencephalic tegmentum and caudate nucleus on experimental tremor in monkeys

Abstract Seven rhesus monkeys with experimental tremor induced by lesions in the ventromedial mesencephalon had topical perfusions of carbachol and atropine in the mesencephalic tegmentum and head of the caudate nucleus through “push-pull” cannulae. Carbachol produced an increase in tremor in the extremities contralateral to the perfusion site. Atropine in the mesencephalic tegmentum arrested tremor also in the contralateral extremities and prevented an increase of tremor produced by carbachol in the caudate nucleus. In two monkeys without tremor, perfusion of carbachol in either the mesencephalic tegmentum or head of the caudate nucleus failed to induce tremor of the type seen in the other monkeys, but instead induced excitation and generalized shivering with occasional rhythmic EMG bursts. We concluded that in the mesencephalic region, where lesions are effective in arresting both experimental tremor and tremor of Parkinsons disease, there is a cholinoceptive structure that participates in the generation of tremor. Such a structure may modify the acetylcholine-dopamine balance in the head of the caudate nucleus that already has been disrupted by lesions in the ventromedial mesencephalon.

Alumina cream-induced epilepsy in cats. III. Wakefulness-sleep modulation of multiple unit activity in the reticular formation

Abstract Quantitative changes in tonic and phasic multiple unit activities (MUA) of the mesencephalic (MRF) and pontine reticular formations (PRF), pyramidal tract (PT) and neck muscles (EMG) during wakefulness (W), slow wave sleep (SWS) and paradoxical sleep (PS) were determined in alumina cream-induced epileptic cats showing two types of EEG/EMG seizures: type B characterized by continuous isolated EEG spikes and EMG jerks (epilepsia partialis continua) and type C characterized by episodic tonic-clonic EEG spikes and EMG jerks (adversive seizures). 1. (1) Tonic PT, MRF and PRF MUA were large during W and PS and low during SWS while EMG MUA was large during W, low during SWS and almost abolished during PS. PT and EMG MUA significantly decreased while MRF and PRF MUA did not change when cats shifted from W to SWS. PT, MRF and PRF MUA significantly increased while EMG MUA decreased from SWS to PS. PRF MUA significantly increased and EMG MUA significantly decreased while PT and MRF MUA did not change from W to PS. 2. (2) During W, type B phasic PT, MRF, PRF and EMG MUA significantly increased time-locked to the onset of isolated EEG spikes. During SWS and PS, PT, MRF and PRF MUA significantly increased while EMG MUA remained unchanged at the onset of EEG spikes. Type B phasic PT MUA significantly decreased when cats shifted from W and PS to SWS, EMG MUA decreased from W to SWS and PS while MRF and PRF did not change systematically through different wakefulness-sleep state shifts. 3. (3) During W, type C phasic PT, MRF and PRF MUA significantly increased 1 sec before while EMG MUA increased 1 sec after the onset of EEG tonic-clonic discharges. During PS, PT, MRF and PRF MUA significantly increased 5-4 sec before, decreased 2–3 sec after and increased 5–6 sec after while EMG MUA remained low and unchanged until it significantly increased 4 sec after the onset of tonic-clonic EEG discharges. PT MUA significantly increased 3 sec before, PRF MUA decreased 3 sec after and EMG MUA decreased 1–4 sec after the onset of tonic-clonic EEG discharges when cats shifted from W and SWS to PS.