Allan Netick

Neuronal activity specific to REM sleep and its relationship to breathing

The search for the neural substrate of a state of consciousness has led to the expectation that there may be neurons which discharge tonically and rhythmically during that state alone. We have now recorded in the cat the first evidence of neurons whose rhythmic discharge is consistent with the hypothesis of a tonically active neural substrate for rapid eye movement (REM) sleep. These neurons, located in the area of gigantocellular and lateral medullary tegmental fields, begin rhythmically discharging simultaneously with the cortical desynchronization at REM sleep onset and cease firing at arousal from REM; they are essentially silent at all other times. Modulations of the discharge rate correlate with the phasic events of REM sleep, such as ataxic breathing and eye movement bursts. In addition, there is a high correlation between their discharge rate and respiratory frequency analyzed on a breath-by-breath basis. The significant rhythmicity of their discharge coupled with high REM selectivity contrasts them with putative REM generators reported by others in the pons and suggests their crucial role in REM generation.

Breathing during sleep and wakefulness in the cat

Abstract Adult cats were equipped with standard electrodes and skull-bolts for chronic sleep recordings with head-restraint. Respiration was monitored with a pneumotachograph connected to a tube which was inserted into the trachea through a chronic fistula. Episodes of breathing in wakefulness (W), nonrapid eye movement (NREM) and rapid eye movement (REM) sleep were recorded and digitized for computer analysis. The combined means and standard errors of the mean for frequency of breathing (f), peak inspiratory airflow rate (PF), tidal volume (V t ) and minute-volume ( e ) were as follows, (1) In NREM, f was lower (25.5 ± 0.35/min) than in W (37.5 ± 1.5) and REM (41.8 ± 1.9). Changes in f across states resulted from changes in both the lengths of inspiration (T i ) and expiration (T e ). The ratio T i /T i +T k progressively increased from W to NREM and from NREM to REM. (2) PF decreased from W (4.324 liter/min) to NREM (3.03 ± 0.04) and REM (2.572 ± 0.05). There was a strong positive correlation between PF and V t . (3) V t was larger in NREM (35.1 ± 0.43 ml) than in W (33.2 ± 0.73) or REM (24.4 ± 0.63). V T and f were positively correlated on a breath-by-breath basis. (4) V e decreased in sleep (W = 1081 ± 25 ml; NREM = 883 ± 9.9: REM = 806 ± 19). Cats were also studied with dead spaces added to the pneumotachograph. Ventilation parameters increased, but the effects of state on breathing, as determined without added dead space, were confirmed.

Behavioral control of breathing in the cat.

Respiration depends upon brainstem neuronal circuits that produce the respiratory rhythm and relay it, via the ventrolateral columns, to motor neurons in the spinal cord. This brainstem system produces respiration automatically, i.e. without conscious effort, and is responsive to chemical and mechanical stimuli that signal imbalances in respiratory homeostasis. In addition to this automatic/metabolic respiratory system, there is a voluntary/behavioral system that controls the respiratory muscles during speaking, breath holding, and other voluntary respiratory acts. It has been proposed that this behavioral system involves corticofugal fibers that bypass the automatic system, course in the dorsolateral columns, and end at the level of the respiratory motor neurons. According to this scheme, the integration of behavioral control with automatic/metabolic control occurs at the level of the motor neurons and not within the automatic system. This proposed scheme has not been investigated experimentally. In the present study, we trained cats to control their respiration and recorded the activity of cells within the automatic system in the medulla during this behavioral control. We trained the animals to terminate inspiration and prolong expiration when a tone sounded. Microelectrode recordings from 40 medullary respiratory neurons showed that most cells, inspiratory and expiratory, became inactive during the behavioral apneic response. The exceptions were some expiratory cells that were activated during the task. These results suggest that the integration of behavioral influences occurs within the automatic system.

Erroneous classification of neuronal activity by the respiratory modulation index

Failure to record respiratory activity in the mesencephalon of the chronic cat led us to analyze the formula (the respiratory modulation index, RMI) used by Hugelin and his colleagues to discriminate respiratory neurons. Using computer simulations, we compared RMI with the analysis of variance (F) and the non-parametric Friedmans test (chi 2). Samples were drawn repeatedly from simulated distributions of neuronal activity and were allocated to successive bins representing the respiratory cycle. Allocations of bins were made randomly so that only a chance relationship existed between the simulated activity and respiratory cycle. These simulations revealed that the RMI erroneously yields values indicative of a respiratory relationship and does so as a function of sample size and the variability and shape of the distribution of non-respiratory activity. Although some of the simulated conditions violated assumptions of the F test and, to a lesser degree, the chi 2, these statistics erred at rates close to the chosen 5% level. When respiratory activity was stimulated, chi 2 and F were more sensitive than RMI in detecting the relationship. We conclude that the high incidence of respiratory activity reported by the Hugelin group is based upon a faulty statistic and is highly questionable.

Multiple resources for processing and storage in short-term working memory

A frequent assumption in cognitive psychology is that performance in decision making and planning is severely restricted by the limited capacity of short-term working memory. Many predictions of this theory have not been supported, possibly because working memory may be composed of multiple resources rather than a single resource. The present experiments study two tasks, both involving memory for digits. Although these tasks can employ the same modality for input and for responding, they appear to differ in their demands for working memory resources. Specifically, the tasks appear to differ in resources required for processing at input, and they also differ in resources in the sense of storage capacity. The results support a version of multiple-resource theory applied to working memory in which resource composition depends on internal mediators even when stimulus and response modality are held constant.

Sleep-related apneic and apneustic breathing following pneumotaxic lesion and vagotomy

Sleep-wakefulness state was found to be a crucial determinant of respiratory pattern in chronic cats with bilateral lesions of the rostral pontine pneumotaxic complex (PC). Lesions resulted in increased TE, TI, and VT in all sleep and waking states. Several state-specific respiratory effects were also observed: (1) comparatively eupneic breathing during alert wakefulness (WI); (2) greatly increased TE in slow wave sleep (SWS); (3) decreased TE during rapid eye movement sleep (REM), relative to SWS; (4) increased tendency for prolonged TI (brief apneusis) during REM. Bilateral vagotomy at 2-5 weeks after PC lesion exaggerated these effects and caused distinct apneusis during REM. The results confirm that the PC is not essential for the occurrence of either rhythmic breathing or for expression of state changes in respiration, although the effects of the PC on breathing in the intact cat may vary as a function of sleep-wakefulness state. It is suggested that other regulatory systems that influence the central respiratory rhythm generator (RRG) are similarly modulated by state, and that variations in respiratory pattern observed following PC lesion and vagotomy are the result of state-dependent changes in the balance between multiple inputs to the RRG.

Hesitations in continuous tracking induced by a concurrent discrete task

Subjects performed continuous, visually guided pursuit tracking with the right hand while giving simultaneous discrete left-hand responses, which were signaled by auditory tones appearing at the average rate of one tone per 30 s. This left-hand secondary task was frequently associated with tracking hesitations lasting 333 ms or longer. The rate of occurrence of these hesitations was about the same when the left-hand response involved a choice between competing responses as when the left hand responded in a previously specified direction. Hesitations occurred for three different mechanical tracking manipulanda using different controlling muscles and appeared to be due to active muscular freezing rather than to relaxation. The rate of hesitations declined with practice, and this improvement in right-hand performance was accompanied by an improvement in performance of the concurrent left-hand response.

Sleep state effects on breathing after spinal cord transection and vagotomy in the cat.

The role of chest wall and vagal afferents on breathing during wakefulness (W), nonrapid eye movement sleep (NREM), and REM sleep was assessed in 16 adult cats implanted with electrodes and skull bolts for sleep recordings with head restraint. Breathing was monitored with a pneumotachograph. Following control recordings establishing characteristic respiratory patterns during each state, cats sustained spinal cord transections at T-1, vagotomies, or both. The transections decreased variability of breathing rate, while vagotomies decreased rate but increased variability and tidal volume. These deafferentations alone or in combination failed to eliminate the major effects of state upon breathing pattern. Different states of consciousness were associated with significant changes on every measured breathing parameter, but the interactions of these effects with the deafferentations were small or nonsignificant. The vagus, however, appears to play its largest role during NREM. We hypothesize that while vagal afference functions during all states to terminate inspiration, during W and REM separate but functionally equivalent mechanisms of central origin supplement the vagus in facilitating the termination of inspiration. The absence of these mechanisms during NREM accounts for the increased vagal influence during this state.